Medicament for treating cough

ABSTRACT

The present invention pertains to a medicament for preventing or treating cough, including, as an active ingredient, a compound having P2X4 receptor antagonistic action, a tautomer, stereoisomer, or pharmaceutically acceptable salt of the compound, or a hydrate or solvate thereof.

This is a continuation of U.S. application Ser. No. 16/979,383, which isa US National Stage entry of PCT/JP2019/010652, filed Mar. 14, 2019,which claims priority to JP App. No. 2018-046152, filed Mar. 14, 2018and JP App. No. 2018-164852, filed Sep. 3, 2018. The disclosure of eachof the above-identified documents is incorporated herein by reference inits entirety.

TECHNICAL FIELD

The present invention relates to a prophylactic or therapeutic agent forcough.

BACKGROUND ART

Cough is an intrinsic biological defense response to a foreign materialand/or pathogen entering the airway. However, excessive (pathological)cough causes a patient's pain and exhaustion.

Cough is grouped, depending on the duration, into acute cough lastingless than 3 weeks, persistent cough lasting from 3 weeks to less than 8weeks, and chronic cough lasting 8 weeks or longer.

The major cause of acute cough is an airway infection including commoncold, and the frequency of the infection decreases as the durationbecomes longer. Infection itself rarely causes chronic cough. Meanwhile,chronic cough is defined such that “the only symptom is cough lasting 8weeks or longer, the cause of which cannot be identified by generalexamination such as an interview, physical examination, routine chestradiograph, and/or spirography.

In addition, pathological cough is grouped into dry cough without phlegmand wet cough with phlegm. The former occurs upon cough hypersensitivityor airway spasm caused by various mechanical/chemical stimuli. Bycontrast, the latter is mainly caused by phlegm-induced mechanicalstimuli (cough to expectorate phlegm).

Antitussive agents can clinically suppress cough by blocking any site ina peripheral or central pathway for cough.

Codeine, which is a central nervous system acting medicament, blocks acommon pathway among cough mechanisms and thus exerts considerableeffects. Nowadays, such a central nervous system acting medicament isoften prescribed.

This may be because the cough mechanisms are largely unclear and eventhe currently revealed mechanisms are still complicated. For instance,there may be tracheal/alveolar inflammation, foreign material, or phlegmaccumulation. In these cases, receptors (cough receptors) at the sitedetect the event to transmit it, via afferent nerves such asglossopharyngeal nerve and superior laryngeal nerve, to a center, whatis called a cough center, where cough reflex in the respiratory centerof medulla oblongata in the brain stem is integrated. When theinformation is transmitted from the cough receptors to the cough center,activity of the central regulatory neural mechanism for respiratorymovement is modulated. The resulting signal is transmitted via efferentnerves such as vagus nerve and phrenic nerve to the diaphragm and thoraxmuscles. Then, a strong expiratory effort occurs, accompanied by a rapidincrease in intrapleural pressure, leading to cough reflux. This is amechanism.

In view of the current findings, representative examples of a coughinduction-related receptor seem to involve rapid adapting receptors(RARs), which are Aδ fiber terminal receptors or receptors at thebronchopulmonary C fiber terminal. ATP (adenosine triphosphate) has beenknown to involve Aδ fiber and C fiber. It has been revealed that ATPdiversely involves pain signal transduction through various ATP receptorsubtypes that are expressed on dorsal root ganglion (DRG) neurons,dorsal horn neurons, spinal microglia, the higher central nervoussystem, and others. ATP receptors are largely classified into anion-channel-type ATP receptor (P2X) and a G protein-coupled ATP receptor(P2Y), which are revealed to have 7 subtypes (P2X1-7) and 8 subtypes(P2Y1, 2, 4, 6, and 11-14), respectively.

Among the ATP receptor subtypes, the P2X receptors are shown to co-existwith, for instance, a capsaicin receptor TRPV1 and be expressed on C andA5 fibers of the dorsal root ganglion nerve (Non Patent Literature 2)

Meanwhile, Kamei and colleagues in Non Patent Literature 1 have reportedthat in an experiment in which guinea pigs were stimulated with citricacid to induce cough (hereinafter, citric acid-induced cough), ATPelicited a concentration-dependent and significant increase and thiseffect was completely inhibited by TNP-ATP inhalation pretreatment butnot by PPADS aerosol.

It has been known that TNP-ATP is a P2X1-4 receptor antagonist and PPADSis a P2X1, 2, 3, 5, or 7 receptor antagonist.

Then, stimulation of P2X receptors in the airway, in particular, P2X4receptor is reportedly suggested to be necessary for augmentingATP-induced cough reflux.

Kamei and colleagues in Non Patent Literature 2 have reported that whenthe possibility of involvement of ATP receptors in the modulation ofcough reflux was investigated, data was obtained that indicated theinvolvement in expression of cough reflux by directly modulatingexcitation of A5 fiber. In addition, the number of coughs that wereinduced by citric acid and were increased depending on the concentrationof ATP was decreased by use of TNP-ATP, which is a P2X-type receptorantagonist. Thus, ATP may increase cough reflux by enhancing, throughATP receptors on the airway, in particular, P2X-type receptors, thesensitivity of RARs or cough receptors, said the report.

Patent Literature 1 discloses a respiratory disease therapeuticincluding a P2X receptor antagonistic compound, and claims 7 and 8further stipulate that “the P2X receptor is P2X4 receptor”.

However, the P2X receptor antagonistic compound is not specificallydisclosed. Regarding the P2X4 receptor antagonistic compound, neitherthe name or the structure and the like of the compound nor informationrequired for manufacture or identification of the compound is disclosed.Here, not every P2X-type receptor antagonist exhibits an antitussiveeffect.

Further, the present applicants have filed P2X4 receptorantagonist-related Japanese Patent Applications, such as PatentLiteratures 2 to 8. Any of the applications neither describes norsuggests the prophylaxis or treatment of cough.

CITATION LIST Patent Literature

-   Patent Literature 1: WO 2005/107804-   Patent Literature 2: WO 2008/023847-   Patent Literature 3: WO 2010/093061-   Patent Literature 4: WO 2012/008478-   Patent Literature 5: WO 2012/014910-   Patent Literature 6: WO 2012/017876-   Patent Literature 7: WO 2013/105608-   Patent Literature 8: WO 2015/005468-   Patent Literature 9: WO 2015/005467

Non Patent Literature

-   Non Patent Literature 1: European Journal of Phaemacology 528,    158-161 (2005)-   Non Patent Literature 2: Folia Pharmacol. Jpn., 131, 429-433 (2008)

SUMMARY OF INVENTION Technical Problem

The present invention addresses the problem of providing a medicamentfor preventing or treating cough. More specifically, provided is amedicament for preventing or treating acute cough, persistent cough, orchronic cough, in particular, chronic cough.

As described above, a central nervous system acting medicament such ascodeine blocks a common pathway among the cough mechanisms and thusexerts a large effect. However, there is a problem of stopping coughthat is necessary as biological defense and should not be stoppedessentially. In addition, the central nervous system acting medicamentis frequently accompanied by side effects such as constipation anddrowsiness caused by its effect on central nervous system except forcough. Further, even use of the maximum dose of codeine is oftenresistant to cough caused by cough variant asthma or gastroesophagealreflux disease. When these matters are taken into consideration, it isunpreferable that the central nervous system acting medicament is usedto block cough. Hence, a more selective means should be used for coughsuppression.

Solution to Problem

The present inventors have conducted intensive research to solve theabove problem and, as a result, have found that compounds having P2X4receptor antagonistic action and represented by general formulas (AI) to(HII) are useful in prophylaxis or treatment of cough. Then, the presentinvention has thus been completed.

Specifically, the present invention provides a medicament for preventingor treating cough, the medicament including, as an active ingredient, acompound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof.

For instance, each compound represented by general formulas (AI) to(HII) below may be used as the compound having P2X4 receptorantagonistic action.

More preferably, a compound represented by general formula (AI), (EI),(FI), or (GI) below may be used as the compound having P2X4 receptorantagonistic action.

The compound having P2X4 receptor antagonistic action acts selectivelyon peripheral P2X4 receptors and can inhibit cough peripherally. Thus,the compound having P2X4 receptor antagonistic action can exert effectson peripheral ATP receptors (P2X4 receptors) such as those on airwaytissues and primary afferent fiber cell bodies (DRG: dorsal rootganglions) that transmit cough reflux stimuli. Accordingly, the compoundmay be useful as a peripheral antitussive agent without direct effectson the cough center present in the medulla oblongata.

A medicament of the present invention may be used for preventing ortreating, for instance, cough, preferably acute cough, persistent cough,or chronic cough and more preferably chronic cough. Further, it ispossible to be used for preventing or treating cough such as a diseaseresponsible for chronic cough including dry cough (e.g., cough caused bycough variant asthma, atopic cough, allergic cough) and wet cough (e.g.,chronic obstructive pulmonary disease, asthma).

From other viewpoints, the present invention provides: use of a compoundhaving P2X4 receptor antagonistic action, a tautomer, stereoisomer, orpharmaceutically acceptable salt of the compound, or a hydrate orsolvate thereof for the manufacture of the above medicament; and amethod for preventing or treating cough, including the step ofadministering, to a mammal including a human, a prophylactically ortherapeutically effective amount of a compound having P2X4 receptorantagonistic action, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof,wherein the cough is selected from dry cough such as cough caused bycough variant asthma, atopic cough, cough caused by gastroesophagealreflux, chemical-induced cough, or allergic cough or wet cough such ascough caused by sinobronchial syndrome, cough caused by chronicbronchitis, cough caused by chronic obstructive pulmonary disease, orcough caused by asthma.

Advantageous Effects of Invention

A medicament of the present invention is useful as a medicament forpreventing or treating cough, preferably acute cough, persistent cough,or chronic cough and more preferably chronic cough, and should befurther highly effective in prophylaxis or treatment of cough such as adisease responsible for chronic cough including dry cough (e.g., coughcaused by cough variant asthma, atopic cough, cough caused bygastroesophageal reflux, chemical-induced cough, or allergic cough) orwet cough (e.g., cough caused by sinobronchial syndrome, cough caused bychronic bronchitis, cough caused by chronic obstructive pulmonarydisease, or cough caused by asthma). The medicament is useful, inparticular, for dry cough, and is especially useful for cough caused bycough variant asthma, atopic cough, or allergic cough.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph showing cough inhibitory action of compound A oncitric acid (0.25 M)-induced cough after compound A was orallyadministered to pretreatment mice.

FIG. 2 is a graph showing an inhibition rate while the rate obtainedfrom the test results in FIG. 1 was 100% when the number of coughs was0.

FIG. 3 is a graph indicating cough inhibitory action of dihydrocodeineon citric acid (0.25 M)-induced cough after 10 mg/kg of dihydrocodeinewas orally administered to pretreatment mice and showing an inhibitionrate while the rate obtained from the test results was 100% when thenumber of coughs was 0.

FIG. 4 is a graph indicating cough inhibitory action of compound A oncitric acid (0.1 M)-induced cough after compound A (0.3 mg/kg) wasorally administered to airway inflammation model mice with airwayinflammation. The stimulation with citric acid (0.1 M) was conducted at1 h after the compound A administration.

FIG. 5 is a graph indicating cough inhibitory action of compound A uponcitric acid (0.25 M) stimulation after airway inflammation model micewith airway inflammation received compound A (10 to 100 μg/mL) byinhalation using a nebulizer. The stimulation with citric acid (0.25 M)was conducted at 4 min after the compound A administration.

FIG. 6 is a graph showing an inhibition rate while the rate obtainedfrom the test results in FIG. 5 was 100% when the number of coughs was0.

FIG. 7 is a graph showing cough inhibitory action of compound A oncitric acid (0.5 M)-induced cough after compound A was orallyadministered to pretreatment guinea pigs.

FIG. 8 is a graph showing an inhibition rate while the rate obtainedfrom the test results in FIG. 7 was 100% when the number of coughs was0.

FIG. 9 is a graph showing cough inhibitory action of compound B oncitric acid (0.5 M)-induced cough after compound B was orallyadministered to pretreatment guinea pigs.

FIG. 10 is a graph showing an inhibition rate while the rate obtainedfrom the test results in FIG. 9 was 100% when the number of coughs was0.

FIG. 11 is a graph indicating cough inhibitory action of compound A oncitric acid (0.25 M)-induced cough after compound A (1.0 mg/kg) wasorally administered to ovalbumin (hereinafter, referred to as“OVA”)-sensitized guinea pigs (OVA-sensitized cough model guinea pigs).The stimulation with citric acid (0.25 M) was conducted at 1 h after thecompound A administration.

FIG. 12 is a graph indicating cough inhibitory action of compound B oncitric acid (0.25 M)-induced cough after compound B (1.0 mg/kg) wasorally administered to OVA-sensitized cough model guinea pigs. Thestimulation with citric acid (0.25 M) was conducted at 1 h after thecompound B administration.

FIG. 13 is a graph showing cough inhibitory action of compounds C and Don citric acid (0.5 M)-induced cough after compounds C and D was orallyadministered to pretreatment guinea pigs.

FIG. 14 is a graph showing an inhibition rate while the rate obtainedfrom the test results in FIG. 13 was 0% when the number of coughs wasneither increased nor decreased and the rate was 100% when the number ofcoughs was 0.

FIG. 15 is a chart indicating action of compound A on contraction oftracheobronchial smooth muscles excised from a guinea pig.

FIG. 16 is a chart indicating action of compound B on contraction oftracheobronchial smooth muscles excised from a guinea pig.

DESCRIPTION OF EMBODIMENTS

A medicament of the present invention may be used as a medicament forpreventing or treating cough and may be used as a medicament for thefollowing use.

A medicament of the present invention may be used as a medicament forpreventing or treating cough, wherein the cough is acute cough,persistent cough, or chronic cough.

A medicament of the present invention may be used as a medicament forpreventing or treating cough, wherein the cough is chronic cough.

A medicament of the present invention may be used as a medicament forpreventing or treating cough, wherein the cough is dry cough that is,for instance, cough caused by cough variant asthma, atopic cough, coughcaused by gastroesophageal reflux, chemical-induced cough, or allergiccough.

A medicament of the present invention may be used as a medicament forpreventing or treating cough, wherein the cough is wet cough that is,for instance, cough caused by sinobronchial syndrome, cough caused bychronic bronchitis, cough caused by chronic obstructive pulmonarydisease, or cough caused by asthma.

It is possible to use, as an active ingredient in a medicament of thepresent invention, a compound represented by any one of the followinggeneral formulas (AI) to (HII), a tautomer, stereoisomer, orpharmaceutically acceptable salt of the compound, or a hydrate orsolvate thereof.

Abbreviations used in, for instance, the following tables are asfollows.

Me: methyl group; Et: ethyl group; Pr: n-propyl group; iPr: isopropylgroup; tBu: tert-butyl group; Ac: acetyl group; and Ph: phenyl group.

In the tables presented below, substituents may be designated withposition numbers of their substitution positions. In addition, todistinguish the apparently identical position numbers in chemicalformulas, a prime “′” may be given to one of the position numbers forconvenience. Nevertheless, as long as the structure can be specifiedunequivocally, the position numbers in the compound name may beexpressed without using the prime.

(A-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (AI):

wherein R^(1A) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,or a phenyl-substituted C₁₋₃ alkyl group,

R^(2A) and R^(3A) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈dialkylamino group, a C₂₋₈ acylamino group, a C₂₋₈ acylamino groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkylsulfonylamino group,a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (the numberof carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoyl group,a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonylgroup, or a sulfamoyl group,

R^(4A) and R^(5A) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, or a phenyl-substituted C₁₋₃ alkyl group,

W^(A) represents an optionally substituted, 5- or 6-memberedheterocyclic ring comprising 1 to 4 atoms of nitrogen as a ringconstituent element, and

when X^(A) is N, Y^(A) is C═O and a double line composed of a solid lineand a dashed line denotes a single bond and

when X^(A) is C, Y^(A) is N and a double line composed of a solid lineand a dashed line denotes a double bond.

(A-2) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (AII):

wherein R^(11A) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,or a phenyl-substituted C₁₋₃ alkyl group,

R^(12A) and R^(13A) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈dialkylamino group, a C₂₋₈ acylamino group, a C₂₋₈ acylamino groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkylsulfonylamino group,a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (the numberof carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoyl group,a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonylgroup, or a sulfamoyl group,

R^(14A) and R^(15A) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, or a phenyl-substituted C₁₋₃ alkyl group, and

W^(1A) represents an optionally substituted, 5- or 6-memberedheterocyclic ring comprising 1 to 4 atoms of nitrogen as a ringconstituent element.

Examples of the C₁₋₈ alkyl group of R^(1A), R^(2A), R^(3A), R^(4A), andR^(5A) or R^(11A), R^(12A), R^(13A), R^(14A), and R^(15A) in generalformula (AI) or (AII) include a methyl, ethyl, propyl, isopropyl, butyl,i-butyl, t-butyl, pentyl or hexyl group.

Examples of the C₂₋₈ alkenyl group of R^(1A) or R^(11A) include an allylgroup.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsin R^(1A), R^(2A), R^(3A), R^(4A), and R^(5A) or R^(11A), R^(12A),R^(13A), R^(14A), and R^(15A) include a methyl, ethyl, propyl,isopropyl, butyl, or t-butyl group substituted with 1 to 3 halogen atomssuch as fluorine, chlorine, or bromine atoms, and preferably atrifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl, or2-fluoroethyl group.

Examples of the phenyl-substituted C₁₋₃ alkyl group of R^(1A), R^(4A),and R^(5A) or R^(11A), R^(14A), and R^(15A) include a benzyl group.

Examples of the C₁₋₈ alkoxy group of R^(2A) and R^(3A) or R^(12A) andR^(13A) include a methoxy, ethoxy, propoxy, isopropoxy, butoxy,i-butoxy, t-butoxy, pentyloxy, or hexyloxy group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsin R^(2A) and R^(3A) or R^(12A) and R^(13A) include a methyl, ethyl,propyl, isopropyl, butyl, or t-butyl group substituted with 1 to 3halogen atoms such as fluorine, chlorine, or bromine atoms, andpreferably a trifluoromethoxy, 2-chloroethoxy, 2-bromoethoxy, or2-fluoroethoxy group.

Examples of the halogen atom of R^(2A) and R^(3A) or R^(12A) and R^(13A)include a fluorine, chlorine, or bromine atom.

Examples of the C₁₋₈ alkylamino group of R^(2A) and R^(3A) or R^(12A)and R^(13A) include a methylamino or ethylamino group.

Examples of the C₁₋₈ dialkylamino group of R^(2A) and R^(3A) or R^(12A)and R^(13A) include a dimethylamino group or a diethylamino group.

Examples of the C₂₋₈ acylamino group of R^(2A) and R^(3A) or R^(12A) andR^(13A) include an acetylamino group.

Examples of the C₂₋₈ acylamino group substituted with 1 to 3 halogenatoms in R^(2A) and R^(3A) or R^(12A) and R^(13A) include atrifluoromethylcarbonylamino group.

Examples of the C₁₋₈ alkylsulfonylamino group of R^(2A) and R^(3A) orR^(12A) and R^(13A) include a methylsulfonylamino group.

Examples of the C₂₋₈ acyl group of R^(2A) and R^(3A) or R^(12A) andR^(13A) include an acetyl group.

Examples of the alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8) of R^(2A) and R^(3A) or R^(12A) andR^(13A) include a methoxycarbonyl group or an ethoxycarbonyl group.

Examples of the C₁₋₈ alkylthio group of R^(2A) and R^(3A) or R^(12A) andR^(13A) include a methylthio group.

Examples of the C₁₋₈ alkylsulfinyl group of R^(2A) and R^(3A) or R^(12A)and R^(13A) include a methylsulfinyl group.

Examples of the C₁₋₈ alkylsulfonyl group of R^(2A) and R^(3A) or R^(12A)and R^(13A) include a methylsulfonyl group.

Examples of the optionally substituted, 5- or 6-membered heterocyclicring comprising 1 to 4 atoms of nitrogen as a ring constituent elementin W^(A) or W^(1A) include tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, imidazole, oxazole, isoxazole, pyrrole,thiazole, pyridine, or pyrrolidine.

Examples of a substituent of the optionally substituted, 5- or6-membered heterocyclic ring comprising 1 to 4 atoms of nitrogen as aring constituent element in W^(A) or W^(1A) include a C₁₋₈ alkyl groupsuch as a methyl or ethyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms such as a trifluoromethyl group, a halogen atom suchas a fluorine atom, a cyano group, an oxo group, or a thioxo group.

In general formula (AI), 1 to 3 R^(2A) or R^(3A) substituents, which arethe same or different, may be present, in a benzene ring having theR^(2A) or R^(3A) substituents. Likewise, in general formula (AII), 1 to3 R^(12A) and R^(13A) substituents, which are the same or different, maybe present, in a benzene ring having the R^(12A) or R^(13A)substituents.

The following compounds are preferable as compounds represented bygeneral formula (AI).

(A-1-1) A compound described in (A-1), wherein W^(A) is tetrazole,1,2,4-triazole, 1,2,3-triazole, 1,2,4-oxadiazole, pyrazole, or imidazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, acyano group, an oxo group, or a thioxo group.

(A-1-2) A compound described in (A-1) or (A-1-1), wherein W^(A) istetrazole, 1,2,4-triazole, or 1,2,3-triazole optionally having asubstituent selected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, or a cyano group.

(A-1-3) A compound described in (A-1) or any of (A-1-1) to (A-1-2),wherein W^(A) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(A-1-4) A compound described in (A-1) or any of (A-1-1) to (A-1-3),wherein W^(A) is tetrazole.

(A-1-5) A compound described in (A-1) or any of (A-1-1) to (A-1-4),wherein R^(1A) is a hydrogen atom or a C₁₋₈ alkyl group.

(A-1-6) A compound described in (A-1) or any of (A-1-1) to (A-1-5),wherein R^(1A) is a hydrogen atom.

(A-1-7) A compound described in (A-1) or any of (A-1-1) to (A-1-6),wherein R^(4A) is a hydrogen atom and R^(5A) is a hydrogen atom or aC₁₋₈ alkyl group.

(A-1-8) A compound described in (A-1) or any of (A-1-1) to (A-1-7),wherein both R^(4A) and R^(5A) are a hydrogen atom.

(A-1-9) A compound described in (A-1) or any of (A-1-1) to (A-1-8),wherein R^(2A) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a carboxylgroup, a C₂₋₈ acyl group, or an alkoxycarbonyl group (the number ofcarbon atoms in an alkoxy moiety is from 1 to 8).

(A-1-10) A compound described in (A-1) or any of (A-1-1) to (A-1-9),wherein R^(2A) is a hydrogen atom.

(A-1-11) A compound described in (A-1) or any of (A-1-1) to (A-1-10),wherein R^(3A) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a carboxylgroup, a C₂₋₈ acyl group, or an alkoxycarbonyl group (the number ofcarbon atoms in an alkoxy moiety is from 1 to 8).

(A-1-12) A compound described in (A-1) or any of (A-1-1) to (A-1-11),wherein R^(3A) is a hydrogen atom.

(A-1-13) A compound described in (A-1) or any of (A-1-1) to (A-1-12),wherein X^(A) is N, Y^(A) is C═O, and the double line composed of asolid line and a dashed line denotes a single bond.

(A-1-14) A compound described in (A-1) or any of (A-1-1) to (A-1-12),wherein X^(A) is C, Y^(A) is N, and the double line composed of a solidline and a dashed line denotes a double bond.

The following compounds are preferable as compounds represented bygeneral formula (AII).

(A-2-1) A compound described in (A-2), wherein W^(A) is tetrazole,1,2,4-triazole, 1,2,3-triazole, 1,2,4-oxadiazole, pyrazole, or imidazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, acyano group, an oxo group, or a thioxo group.

(A-2-2) A compound described in (A-2) or (A-2-1), wherein W^(A) istetrazole, 1,2,4-triazole, or 1,2,3-triazole optionally having asubstituent selected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, or a cyano group.

(A-2-3) A compound described in (A-2) or any of (A-2-1) to (A-2-2),wherein W^(A) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(A-2-4) A compound described in (A-1) or any of (A-2-1) to (A-2-3),wherein W^(A) is tetrazole.

(A-2-5) A compound described in (A-1) or any of (A-2-1) to (A-2-4),wherein R^(1A) is a hydrogen atom or a C₁₋₈ alkyl group.

(A-2-6) A compound described in (A-1) or any of (A-2-1) to (A-2-5),wherein R^(lA) is a hydrogen atom.

(A-2-7) A compound described in (A-1) or any of (A-2-1) to (A-2-6),wherein R^(4A) is a hydrogen atom and R^(5A) is a hydrogen atom or aC₁₋₈ alkyl group.

(A-2-8) A compound described in (A-1) or any of (A-2-1) to (A-2-7),wherein both R^(4A) and R^(5A) are a hydrogen atom.

(A-2-9) A compound described in (A-1) or any of (A-2-1) to (A-2-8),wherein R^(2A) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a carboxylgroup, a C₂₋₈ acyl group, or an alkoxycarbonyl group (the number ofcarbon atoms in an alkoxy moiety is from 1 to 8).

(A-2-10) A compound described in (A-1) or any of (A-2-1) to (A-2-9),wherein R^(2A) is a hydrogen atom.

(A-2-11) A compound described in (A-1) or any of (A-2-1) to (A-2-10),wherein R^(3A) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a carboxylgroup, a C₂₋₈ acyl group, or an alkoxycarbonyl group (the number ofcarbon atoms in an alkoxy moiety is from 1 to 8).

(A-2-12) A compound described in (A-1) or any of (A-2-1) to (A-2-11),wherein R^(3A) is a hydrogen atom.

The following shows representative compounds included in general formula(AI).

<Representative Compound A-100>

wherein R^(1A), R^(4A), R^(5A), and W^(A), and W^(A) substitutionpositions are as described in Tables 1 to 3.

In Tables 1 to 3, each W^(A) substitution position indicates asubstitution position on a benzene ring. Specifically, positions 2, 3,and 4 in the tables correspond to positions 2′, 3′, and 4′,respectively, in the formula of representative compound A-100.

TABLE 1 W^(A) SUBSTITUTION R^(1A) POSITION W^(A) R^(4A)/R^(5A) H 2-1H-Tetrazol-5-yl H/H H 3- 1H-Tetrazol-5-yl H/H H 3-(1-Methyl-1H-tetrazol)-5-yl H/H H 4- 1H-Tetrazol-5-yl H/H Me 3-1H-Tetrazol-5-yl H/H Me 3- 1H-Tetrazol-5-yl Me/H Bn 3- 1H-Tetrazol-5-ylH/H H 3- 1H-Tetrazol-5-yl H/H H 3- 1H-Tetrazol-5-yl Me/Me H 3-(1,2,3-Triazol)-5-yl H/H H 3- (1,2,4-Triazol)-3-yl H/H H 4-(1,2,4-Triazol)-3-yl H/H

TABLE 2 W^(A) SUBSTITUTION R^(1A) POSITION W^(A) R^(4A)/R^(5A) H 2-(1,2,4-Triazol)-1-yl H/H H 3- (1,2,4-Triazol)-1-yl H/H H 3-[5-(Trifluoromethyl)-1,2,4-triazol]-3-yl H/H H 3-[5-(Trifluoromethyl)-1,2,4-triazol]-3-yl Et/H H 3-[5-Fluoro-1,2,3-triazol]-4-yl H/H H 3- [5-Fluoro-1,2,3-triazol]-4-ylMe/Me H 3- [5-Cyano-1,2,3-triazol]-4-yl H/H H 4- 1H-Imidazol-1-yl H/H H4- 1H-Imidazol-1-yl Pr/H H 3- 1H-Imidazol-2-yl H/H H 3- 1H-Imidazol-4-ylH/H H 3- Imidazolin-2-yl H/H

TABLE 3 W^(A) SUBSTITUTION R^(1A) POSITION W^(A) R^(4A)/R^(5A) H 2-Pyrazol-3-yl H/H H 3- Pyrazol-4-yl H/H H 3- Pyrazol-5-yl Me/H H 3-(1,2,4-Oxadiazol)-3-yl H/H H 3- (1,3,4-Oxadiazol)-2-yl H/H H 3-(5-Oxo-1,2,4-oxadiazol)-3-yl H/H H 3- Pyrrol-1-yl H/H H 4-Pyrrolidin-2-yl H/H Me 4- Pyrrolidin-2-yl Me/H H 4- (1,3-Oxazol)-5-ylH/H H 3- (1,3-Oxazol)-5-yl H/H H 2- (1,3-Thiazol)-5-yl H/H

<Representative Compound A-200>

wherein R^(1A), R^(2A), R^(4A), R^(5A), and W^(A), and W^(A)substitution positions are as described in Tables 4 and 5.

In tables 4 and 5, each W^(A) substitution position indicates asubstitution position on a benzene ring. Specifically, positions 2, 3,and 4 in the tables correspond to positions 2′, 3′, and 4′,respectively, in the formula of representative compound A-200.

TABLE 4 W^(A) SUBSTITUTION R^(1A) R^(2A) POSITION W^(A) R^(4A)/R^(5A) H4-OH 3- 1H-Tetrazol-5-yl H/H H 4-OMe 3- 1H-Tetrazol-5-yl H/H Me 2-Cl 3-1H-Tetrazol-5-yl H/H H 2,6-Cl 3- 1H-Tetrazol-5-yl H/H H 4-F 3-1H-Tetrazol-5-yl H/H H 4-Br 3- 1H-Tetrazol-5-yl Et/H H 3-OMe 4-(1-Methyl-1H-tetrazol)-5-yl H/H H 4-Me 3- 1H-Tetrazol-5-yl H/H

TABLE 5 W^(A) SUBSTITUTION R^(1A) R^(2A) POSITION W^(A) R^(4A)/R^(5A) H4-Cl 3- (1,2,3-Triazol)-5-yl Me/H H 4-CF₃ 3- (1,2,3-Triazol)-5-yl H/H H3-SMe 4- (1,2,4-Triazol)-1-yl H/H H 3-SO₂Me 4- 1H-Imidazol-1-yl H/H H3-NHSO₂Me 4- 1H-Imidazol-1-yl H/H H 4-OMe 3- 1H-Imidazol-4-yl H/H H 4-F2- Pyrazol-3-yl H/H

<Representative Compound A-300>

wherein R^(1A), R^(2A), R^(3A), R^(4A), R^(5A), and W^(A), and W^(A)substitution positions are as described in Tables 6 and 7.

In Tables 6 and 7, each W^(A) substitution position indicates asubstitution position on a benzene ring. Specifically, positions 3 and 4in the tables correspond to positions 3′ and 4′, respectively, in theformula of representative compound A-300.

TABLE 6 W^(A) SUBSTITUTION R^(4A)/ R^(1A) R^(2A) POSITION W^(A) R^(3A)R^(5A) H H 3- 1H-Tetrazol-5-yl 9-Br H/H H 4-OMe 3- 1H-Tetrazol-5-yl 9-ClH/H H 4-OH 3- 1H-Tetrazol-5-yl 10-OMe H/H H 2-Cl 3- 1H-Tetrazol-5-yl9-Br H/H H 2,6-Cl 3- 1H-Tetrazol-5-yl 9-Me H/H H H 3- 1H-Tetrazol-5-yl10-Cl Me/H H 3-OMe 4- (1-Methyl-1H- 9-GF₃ H/H tetrazol)-5-yl

TABLE 7 W^(A) SUBSTITUTION R^(1A) R^(2A) POSITION W^(A) R^(3A)R^(4A)/R^(5A) H 4-Me 3- 1H-Tetrazol-1-yl 9-CN Pr/H Me H 3-(1,2,3-Triazol)-5-yl 9-OH H/H Et H 3- (1,2,3-Triazol)-5-yl 10-F H/H H3-Br 4- (1,2,4-Triazol)-1-yl 9-SMe H/H Allyl H 4- 1H-Imidazol-1-yl 8-OMeH/H H H 3- 1H-Imidazol-1-yl 10-OMe Me/Me

<Representative Compound A-400>

wherein W^(A) and W^(A) substitution positions are as described in Table8.

In Table 8, each W^(A) substitution position indicates a substitutionposition on a benzene ring. Specifically, positions 3 and 4 in the tablecorrespond to positions 3′ and 4′, respectively, in the formula ofrepresentative compound A-400.

TABLE 8 W^(A) SUBSTITUTION POSITION W^(A) 3- 1H-Tetrazol-5-yl 4-1H-Tetrazol-5-yl 3- 5-Thioxo-1,2,4-oxadiazol-3-yl

(B-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (BI):

wherein R^(1B) and R^(2B) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, aC₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,

R^(3B) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or aphenyl-substituted C₁₋₃ alkyl group,

R^(4B) and R^(5B) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, or a phenyl-substituted C₁₋₃ alkyl group,

R^(6B) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, aC₂₋₈ acylamino group, a C₂₋₈ acylamino group substituted with 1 to 3halogen atoms, a C₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈acyl group, an alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8), a carbamoyl group, a C₁₋₈ alkylthiogroup, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, asulfamoyl group, an optionally substituted phenyl group, or anoptionally substituted heterocyclic ring group,

optionally contains, as ring constituent elements, 1 to 2 heteroatomsselected from N, S, or O and represents a 5- to 8-membered non-aromaticring condensed with a benzene ring at positions 1 and 2,

represents an aromatic ring selected from a benzene ring, a naphthalenering, a thiophene ring, a pyridine ring, a pyrimidine ring, an indolering, an indazole ring, a benzotriazole ring, a benzisoxazole ring, abenzimidazole ring, or a quinoline ring,

Z^(B) represents O or S, and

when X^(B) is N, Y^(B) is C═O or C═S and a double line composed of asolid line and a dashed line denotes a single bond and

when X^(B) is C, Y^(B) is N and a double line composed of a solid lineand a dashed line denotes a double bond.

(B-2) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (BII):

wherein R^(11B) and R^(12B) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, aC₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,

R^(13B) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or aphenyl-substituted C₁₋₃ alkyl group,

R^(14B) and R^(15B) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, or a phenyl-substituted C₁₋₃ alkyl group,

R^(16B) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, aC₂₋₈ acylamino group, a C₂₋₈ acylamino group substituted with 1 to 3halogen atoms, a C₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈acyl group, an alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8), a carbamoyl group, a C₁₋₈ alkylthiogroup, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, asulfamoyl group, an optionally substituted phenyl group, or anoptionally substituted heterocyclic ring group,

optionally contains, as ring constituent elements, 1 to 2 heteroatomsselected from N, S, or O and represents a 5- to 8-membered non-aromaticring condensed with a benzene ring at positions 1 and 2,

represents an aromatic ring selected from a benzene ring, a naphthalenering, a thiophene ring, a pyridine ring, a pyrimidine ring, an indolering, an indazole ring, a benzotriazole ring, a benzisoxazole ring, abenzimidazole ring, or a quinoline ring, and

Z^(1B) and Z^(2B) are the same or different and represent O or S.

(B-3) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (BIII):

wherein R^(21B) and R^(22B) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, aC₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,

R^(23B) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or aphenyl-substituted C_(Z)-3 alkyl group, R^(24B) and R^(25B) are the sameor different and represent a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, or aphenyl-substituted C₁₋₃ alkyl group,

R^(26B) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, aC₂₋₈ acylamino group, a C₂₋₈ acylamino group substituted with 1 to 3halogen atoms, a C₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈acyl group, an alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8), a carbamoyl group, a C₁₋₈ alkylthiogroup, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, asulfamoyl group, an optionally substituted phenyl group, or anoptionally substituted heterocyclic ring group, and

p^(B) is 0 or 1.

Examples of the C₁₋₈ alkyl group of R^(1B), R^(2B), R^(3B), R^(4B),R^(5B), or R^(6B) in general formula (BI) include a methyl, ethyl,propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl, or hexyl group.

Examples of the C₂₋₈ alkenyl group of R^(1B), R^(2B), R^(3B), or R^(6B)include an allyl group.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsin R^(1B), R^(2B), R^(3B), R^(4B), R^(5B), or R^(6B) include a methyl,ethyl, propyl, isopropyl, butyl, or t-butyl group substituted with 1 to3 halogen atoms such as fluorine, chlorine, or bromine atoms, andpreferably a trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl,or 2-fluoroethyl group.

Examples of the phenyl-substituted C₁₋₃ alkyl group of R^(3B), R^(4B),or R^(5B) include a benzyl group.

Examples of the C₁₋₈ alkoxy group of R^(1B), R^(2B), or R^(6B) include amethoxy, ethoxy, propoxy, isopropoxy, butoxy, i-butoxy, t-butoxy,pentyloxy, or hexyloxy group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsin R^(1B), R^(2B), or R^(6B) include a methoxy, ethoxy, propoxy,isopropoxy, butoxy, or t-butoxy group substituted with 1 to 3 halogenatoms such as fluorine, chlorine, or bromine atoms, and preferably atrifluoromethoxy, chloromethoxy, 2-chloroethoxy, 2-bromoethoxy, or2-fluoroethoxy group.

Examples of the halogen atom of R^(1B), R^(2B), R^(4B), R^(5B), orR^(6B) include a fluorine, chlorine, or bromine atom.

Examples of the C₁₋₈ alkylamino group of R^(1B), R^(2B), or R^(6B)include a methylamino or ethylamino group.

Examples of the C₂₋₈ dialkylamino group of R^(1B), R^(2B), or R^(6B)include a dimethylamino or diethylamino group.

Examples of the C₂₋₈ acylamino group of R^(1B), R^(2B), or R^(6B)include an acetylamino group.

Examples of the C₂₋₈ acylamino group substituted with 1 to 3 halogenatoms in R^(1B), R^(2B), or R^(6B) include atrifluoromethylcarbonylamino group.

Examples of the C₁₋₈ alkylsulfonylamino group of R^(1B), R^(2B), orR^(6B) include a methylsulfonylamino group.

Examples of the C₂₋₈ acyl group of R^(1B), R^(2B), or R^(6B) include anacetyl group.

Examples of the alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8) of R^(1B), R^(2B), or R^(6B) include amethoxycarbonyl group or an ethoxycarbonyl group.

Examples of the C₁₋₈ alkylthio group of R^(1B), R^(2B), or R^(6B)include a methylthio group.

Examples of the C₁₋₈ alkylsulfinyl group of R^(1B), R^(2B), or R^(6B)include a methylsulfinyl groups.

Examples of the C₁₋₈ alkylsulfonyl group of R^(1B), R^(2B), or R^(6B)include a methylsulfonyl group.

Examples of a preferable substituent of the optionally substitutedphenyl group of R^(6B) include a C₁₋₈ alkyl group such as a methyl orethyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atomssuch as a trifluoromethyl group, a halogen atom such as a fluorine atom,or a cyano group.

Examples of a preferable heterocyclic ring group for the optionallysubstituted heterocyclic ring group of R^(6B) include a tetrazolyl,triazolyl, pyridyl, imidazolyl, oxazolyl or thiazolyl group and furtheroptionally include an oxadiazole group.

Examples of a preferable substituent of the optionally substitutedheterocyclic ring group of R^(6B) include a C₁₋₈ alkyl group such as amethyl or ethyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms such as a trifluoromethyl group, a halogen atom such as afluorine atom, a cyano group, or oxo and further optionally include aphenyl group.

Examples of

include tetrahydronaphthalene, indane, indoline, tetrahydroquinoline, ortetrahydroisoquinoline.

In general formula (BI), R^(1B), R^(2B), or R^(6B) substituents, whichare the same or different, may be present, in a ring having the R^(1B),R^(2B), or R^(6B) substituents.

Regarding the above listed examples, for R^(1B) to R^(6B) in generalformula (BI), comprising a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, aphenyl-substituted C_(Z-3) alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, aC₁₋₈ alkylamino group, a C₁₋₈ dialkylamino, a C₂₋₈ acylamino group, aC₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, a C₂₋₈ acyl group, an alkoxycarbonyl group(the number of carbon atoms in an alkoxy moiety is from 1 to 8), a C₁₋₈alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group,an optionally substituted phenyl group, or an optionally substitutedheterocyclic ring group, the same applies to R^(11B) to R^(16B) ingeneral formula (BII) and R^(21B) to R^(26B) in general formula (BIII).

Likewise, regarding the optionally substituted heterocyclic ring groupof R^(16B) in general formula (BII) or R^(26B) in general formula(BIII), examples of the substituent include a C₁₋₈ alkyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a C₁₋₈ alkylamino group, and a C₂₋₈ dialkylamino group, examplesof which are included in those listed for R^(1B) to R^(6B) in generalformula (BI).

Examples of

include tetrahydronaphthalene, indane, indoline, tetrahydroquinoline, ortetrahydroisoquinoline.

In general formula (BII), R^(11B), R^(12B), or R^(16B) substituents,which are the same or different, may be present, in a benzene ringhaving the R^(11B), R^(12B), or R^(16B) substituents.

In general formula (BIII), R^(21B), R^(22B), or R^(26B) substituents,which are the same or different, may be present in a benzene ring havingthe R^(21B), R^(22B), or R^(26B) substituents.

The following compounds are preferable as compounds included in generalformula (BI).

(B-1-1) A compound described in (B-1), wherein R^(1B) is a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, or aC₂₋₈ acylamino group.

(B-1-2) A compound described in (B-1) or (B-1-1), wherein R^(2B) is ahydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, or a C₂₋₈ acylaminogroup substituted with 1 to 3 halogen atoms.

(B-1-3) A compound described in (B-1) or any of (B-1-1) or (B-1-2),wherein R^(3B) is a hydrogen atom, a C₁₋₈ alkyl group, or a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms.

(B-1-4) A compound described in (B-1) or any of (B-1-1) to (B-1-3),wherein R^(4B) and R^(5B) are the same or different and are a hydrogenatom, a C₁₋₈ alkyl group, or a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms.

(B-1-5) A compound described in (B-1) or any of (B-1-1) to (B-1-4),wherein R^(6B) is a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, oran optionally substituted heterocyclic ring group.

(B-1-6) A compound described in (B-1) or any of (B-1-1) to (B-1-5),wherein R^(6B) is a 5- or 6-membered heterocyclic ring comprising 1 to 4atoms of nitrogen as a ring constituent element.

(B-1-7) A compound described in (B-1) or any of (B-1-1) to (B-1-6),wherein R^(6B) is a tetrazolyl, triazolyl, pyridyl, pyrazolyl,oxadiazolyl, isoxazolyl, pyrrolyl, pyrrolidinyl, imidazolyl, oxazolyl,or thiazolyl group optionally having a substituent selected from a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group.

(B-1-8) A compound described in (B-1) or any of (B-1-1) to (B-1-7),wherein R^(6B) is a tetrazolyl, triazolyl, pyridyl, imidazolyl,oxazolyl, or thiazolyl group optionally having a substituent selectedfrom a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a cyanogroup, or an amino group.

(B-1-9) A compound described in (B-1) or any of (B-1-1) to (B-1-8),wherein R^(6B) is tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, or imidazole optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, a cyano group, an oxo group, or athioxo group.

(B-1-10) A compound described in (B-1) or any of (B-1-1) to (B-1-9),wherein R^(6B) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(B-1-11) A compound described in (B-1) or any of (B-1-1) to (B-1-9),wherein R^(6B) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(B-1-12) A compound described in (B-1) or any of (B-1-1) to (B-1-11),wherein R^(6B) is tetrazole.

(B-1-13)

A compound described in (B-1) or any of (B-1-1) to (B-1-12), wherein

is tetrahydronaphthalene, indane, indoline, tetrahydroquinoline, ortetrahydroisoquinoline.

(B-1-14)

A compound described in (B-1) or any of (B-1-1) to (B-1-13), wherein

is a benzene ring.

(B-1-15) A compound described in (B-1) or any of (B-1-1) to (B-1-14),wherein X^(B) is N, Y^(B) is C═O, and the double line composed of asolid line and a dashed line denotes a single bond.

(B-1-16) A compound described in (B-1) or any of (B-1-1) to (B-1-14),wherein X^(B) is C, Y^(B) is N, and the double line composed of a solidline and a dashed line denotes a double bond.

(B-1-17) A compound described in (B-1) or any of (B-1-1) to (B-1-16),wherein Z^(B) is O.

The following compounds are preferable as compounds included in generalformula (BII).

(B-2-1) A compound described in (B-2), wherein R^(11B) is a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, or aC₂₋₈ acylamino group.

(B-2-2) A compound described in (B-2) or (B-2-1), wherein R^(12B) is ahydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, or a C₂₋₈ acylaminogroup substituted with 1 to 3 halogen atoms.

(B-2-3) A compound described in (B-2) or any of (B-2-1) or (B-2-2),wherein R^(13B) is a hydrogen atom, a C₁₋₈ alkyl group, or a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms.

(B-2-4) A compound described in (B-2) or any of (B-2-1) to (B-2-3),wherein R^(14B) and R^(15B) are the same or different and are a hydrogenatom, a C₁₋₈ alkyl group, or a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms.

(B-2-5) A compound described in (B-2) or any of (B-2-1) to (B-2-4),wherein R^(16B) is a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, oran optionally substituted heterocyclic ring group.

(B-2-6) A compound described in (B-2) or any of (B-2-1) to (B-2-5),wherein R^(16B) is a 5- or 6-membered heterocyclic ring comprising 1 to4 atoms of nitrogen as a ring constituent element.

(B-2-7) A compound described in (B-2) or any of (B-2-1) to (B-2-6),wherein R^(16B) is a tetrazolyl, triazolyl, pyridyl, pyrazolyl,oxadiazolyl, isoxazolyl, pyrrolyl, pyrrolidinyl, imidazolyl, oxazolyl,or thiazolyl group optionally having a substituent selected from a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group.

(B-2-8) A compound described in (B-2) or any of (B-2-1) to (B-2-7),wherein R^(16B) is a tetrazolyl, triazolyl, pyridyl, imidazolyl,oxazolyl, or thiazolyl group optionally having a substituent selectedfrom a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a cyanogroup, or an amino group.

(B-2-9) A compound described in (B-2) or any of (B-2-1) to (B-2-8),wherein R^(16B) is tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, or imidazole optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, a cyano group, an oxo group, or athioxo group.

(B-2-10) A compound described in (B-2) or any of (B-2-1) to (B-2-9),wherein R^(16B) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(B-2-11) A compound described in (B-2) or any of (B-2-1) to (B-2-9),wherein R^(16B) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(B-2-12) A compound described in (B-2) or any of (B-2-1) to (B-2-11),wherein R^(16B) is tetrazole.

(B-2-13)

A compound described in (B-2) or any of (B-2-1) to (B-2-12), wherein

is tetrahydronaphthalene, indane, indoline, tetrahydroquinoline, ortetrahydroisoquinoline.

(B-2-14)

A compound described in (B-2) or any of (B-2-1) to (B-2-13), wherein

is a benzene ring.

(B-2-15) A compound described in (B-2) or any of (B-2-1) to (B-2-14),wherein both Z^(1B) and Z^(2B) are O.

The following compounds are preferable as compounds represented bygeneral formula (BIII).

(B-3-1) A compound described in (B-3), wherein R^(21B) is a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, or aC₂₋₈ acylamino group.

(B-3-2) A compound described in (B-3) or (B-3-1), wherein R^(22B) is ahydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, or a C₂₋₈ acylaminogroup substituted with 1 to 3 halogen atoms.

(B-3-3) A compound described in (B-3) or any of (B-3-1) or (B-3-2),wherein R^(23B) is a hydrogen atom, a C₁₋₈ alkyl group, or a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms.

(B-3-4) A compound described in (B-3) or any of (B-3-1) to (B-3-3),wherein R^(24B) and R^(25B) are the same or different and are a hydrogenatom, a C₁₋₈ alkyl group, or a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms.

(B-3-5) A compound described in (B-3) or any of (B-3-1) to (B-3-4),wherein R^(26B) is a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, oran optionally substituted heterocyclic ring group.

(B-3-6) A compound described in (B-3) or any of (B-3-1) to (B-3-5),wherein R^(26B) is a 5- or 6-membered heterocyclic ring comprising 1 to4 atoms of nitrogen as a ring constituent element.

(B-3-7) A compound described in (B-3) or any of (B-3-1) to (B-3-6),wherein R^(26B) is a tetrazolyl, triazolyl, pyridyl, pyrazolyl,oxadiazolyl, isoxazolyl, pyrrolyl, pyrrolidinyl, imidazolyl, oxazolyl,or thiazolyl group optionally having a substituent selected from a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group.

(B-3-8) A compound described in (B-3) or any of (B-3-1) to (B-3-7),wherein R^(26B) is a tetrazolyl, triazolyl, pyridyl, imidazolyl,oxazolyl, or thiazolyl group optionally having a substituent selectedfrom a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a cyanogroup, or an amino group.

(B-3-9) A compound described in (B-3) or any of (B-3-1) to (B-3-8),wherein R^(26B) is tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, or imidazole optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, a cyano group, an oxo group, or athioxo group.

(B-3-10) A compound described in (B-3) or any of (B-3-1) to (B-3-9),wherein R^(26B) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(B-3-11) A compound described in (B-3) or any of (B-3-1) to (B-3-10),wherein R^(26B) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(B-3-12) A compound described in (B-3) or any of (B-3-1) to (B-3-11),wherein R^(26B) is tetrazole.

Note that R^(3B) in general formula (BI), R^(13B) in general formula(BII), or R^(23B) in general formula (BIII) may be a C₂₋₈ acyl groupsuch as acetyl.

In addition, R^(6B) in general formula (BI), R^(16B) in general formula(BII), or R^(26B) in general formula (BIII) may be a C₃₋₈alkoxycarbonylamino group such as a tert-butoxycarbonylamino group.

Further,

in general formula (BI)

or

in general formula (BII)

may be 2,3-dihydrobenzo[1,4]dioxin.

The following shows representative compounds included in general formula(BI).

<Representative Compound B-100>

wherein A^(B)-B^(B)-D^(B)-E^(B), R^(23B), R^(24B), R^(25B), and R^(26B)are as described in Tables 9 to 11.

TABLE 9 A^(B)-B^(B)-D^(B)-E^(B) R^(23B) R^(24B)/R^(25B) R^(26B)CH₂CH₂CH₂CH₂ H H/H 3-CN CH₂CH₂CH₂CH₂ H H/H 3-OH CH₂CH₂CH₂CH₂ H H/H3-CO₂H CH₂CH₂CH₂CH₂ H H/H 3-CONH₂ C(CH₃)₂CH₂CH₂CH₂ H H/H 3,4-OMeCH₂C(CH₃)₂CH₂CH₂ Me H/H 3,4-OMe CH₂CH₂C(CH₃)₂CH₂ Et H/H 3-OH, 4-FCH₂CH₂CH₂CH₂ H H/H 3-NH₂ NHCH₂CH₂CH₂ H H/H 3-NHMe NMeCH₂CH₂CH₂ H H/H3-CF₃ OCH₂CH₂O H H/H 3-NHCH₂CF₃ OCH₂CH₂O Me H/H 2-OH, 3-OHC(CH₃)₂CH₂CH₂C(CH₃)₂ Et H/H 3,4,5-Me

TABLE 10 A^(B)-B^(B)-D^(B)-E^(B) R^(23B) R^(24B)/R^(25B) R^(26B)CH₂CH₂CH₂CH₂ H Me/H 4-OH CH₂CH₂CH₂CH₂ H Me/Me 4-NH₂ CH₂CH₂CH₂CH₂ H Pr/H4-NO₂ C(CH₃)₂CH₂CH₂CH₂ H H/H 4-CN CH₂C(CH₃)₂CH₂CH₂ Me CF₃/H 4-PhCH₂CH₂C(CH₃)₂CH₂ Et H/H 4-CH₂OH CH₂CH₂CH₂CH₂ H H/H 3-CH₂OH NHCH₂CH₂CH₂ HH/H 3-Ac NMeCH₂CH₂CH₂ H H/H 3,5-OMe OCH₂CH₂O H H/H 3-OH, 4-NH₂ OCH₂CH₂OMe H/H 3-CH₂NH₂ C(CH₃)₂CH₂CH₂C(CH₃)₂ Et H/H 3-SO₂CH₃ CH₂CH₂CH₂CH₂ H Me/H3-iPr CH₂CH₂CH₂CH₂ H Me/H 3-NMe₂

TABLE 11 A^(B)-B^(B)-D^(B)-E^(B) R^(23B) R^(24B)/R^(25B) R^(26B)CH₂CH₂CH₂CH₂ H Me/H 3-Ac C(CH₃)₂CH₂CH₂CH₂ H Pt/H 3,4-NH₂CH₂C(CH₃)₂CH₂CH₂ H H/H NHMe CH₂CH₂C(CH₃)₂CH₂ Et H/H 3-NHCH₂CF₃CH₂CH₂CH₂CH₂ H H/H 3-NHAc NHCH₂CH₂CH₂ H H/H 3-SO₂Me NMeCH₂CH₂CH₂ H H/H4-Me OCH₂CH₂O H H/H 4-iPr OCH₂CH₂O Me H/H 3-Ph C(CH₃)₂CH₂CH₂C(CH₃)₂ EtH/H 3-F, 4-OH CH₂CH₂CH₂CH₂ Ac H/H 3-F, 4-OMe CH₂CH₂CH₂CH₂ H Me/H 4-NHEt

<Representative Compound B-200>

wherein A^(B)-B^(B)-D^(B)-E^(B), R^(24B), R^(25B), R^(26B), and R^(27B)are as described in Tables 12 to 14; and the “Position” in the tablesindicates a R^(26B) substitution position.

TABLE 12 R^(24B)/ A^(B)-B^(B)-D^(B)-E^(B) R^(25B) Position R^(26B)R^(27B) CH₂CH₂CH₂CH₂ H/H 3 1H-Tetrazol-5-yl H C(CH₃)₂CH₂CH₂CH₂ H/H 31H-Tetrazol-5-yl H C(CH₃)₂CH₂CH₂CH₂ H/H 3 1H-Tetrazol-1-yl 4-FC(CH₃)₂CH₂CH₂C(CH₃)₂ H/H 3 2-Methyl-2H-tetrazol- 3-F 5-ylCH₂CH₂C(CH₃)₂CH₂ H/H 3 1,2,3-Triazol-5-yl 2-F CH₂CH₂CH₂CH₂ H/H 31,2,4-Triazol-3-yl H NHCH₂CH₂CH₂ H/H 3 5-(Trifluoromethyl)- H1,2,4-triazol-3-yl NMeCH₂CH₂CH₂ H/H 4 1H-Imidazol-1-yl H OCH₂CH₂O H/H 41H-Imidazol-2-yl H OCH₂CH₂O H/H 3 5-Cyano-1H-1,2,3- H triazol-4-ylC(CH₃)₂CH₂CH₂C(CH₃)₂ H/H 3 1-Methyl-1H- H tetrazol-5-yl CH₂CH₂CH₂CH₂Me/H 3 Pyrazol-3-yl 4-OH CH₂CH₂CH₂CH₂ Me/Me 3 Pyrazol-4-yl H

TABLE 13 R^(24B)/ A^(B)-B^(B)-D^(B)-E^(B) R^(25B) Position R^(26B)R^(27B) C(CH₃)₂CH₂CH₂CH₂ H/H 3 5-Oxo-1,2,4- 4-NH₂ oxadiazol-3-ylCH₂C(CH₃)₂CH₂CH₂ CF₃/H 3 1,2,4-Oxadiazol-3-yl H CH₂CH₂C(CH₃)₂CH₂ H/H 31,3,4-Oxadiazol-2-yl 4-F CH₂CH₂CH₂CH₂ H/H 4 Pyrrol-1-yl 3-F NHCH₂CH₂CH₂H/H 4 Pyrrolidin-2-yl H NMeCH₂CH₂CH₂ H/H 2 1,3-Oxazol-5-yl H OCH₂CH₂OH/H 3 1,3-Thiazol-5-yl H OCH₂CH₂O H/H 3 5-(Trifluoromethyl)- H1H-imidazol-2-yl C(CH₃)₂CH₂CH₂C(CH₃)₂ H/H 3 5-Chloro-1H- 4-OHimidazol-2-yl

TABLE 14 R^(24B)/ A^(B)-B^(B)-D^(B)-E^(B) R^(25B) Position R^(26B)R^(27B) CH₂CH₂CH₂CH₂ Me/H 4 5-Methyl-1H- 4-NH₂ imidazol-2-ylCH₂CH₂CH₂CH₂ Me/H 4 5-Amino-1H- 3-F imidazol-2-yl CH₂CH₂CH₂CH₂ Me/H 32-Ethyl-2H-tetrazol-5-yl H C(CH₃)₂CH₂CH₂CH₂ Pr/H 32-(2,2,2-Trifluoroethyl)- 2,6-F 2H-tetrazol-5-yl CH₂C(CH₃)₂CH₂CH₂ H/H 31,3-Oxazol-2-yl H CH₂CH₂C(CH₃)₂CH₂ H/H 3 1,3-Thiazol-2-yl H CH₂CH₂CH₂CH₂H/H 4 3,5-Dimethylisoxazol- H 4-yl NH₂CH₂CH₂NH H/H 3 3-Methyl-1,2,4- Hoxadiazol-5-yl

<Representative Compound B-300>

wherein A^(B)-B^(B)-D^(B)-E^(B), R^(24B), R^(25B), and T^(0B) are asdescribed in Tables 15 to 17.

TABLE 15 A^(B)-B^(B)-D^(B)-E^(B) R^(24B)/R^(25B) T^(OB) CH₂CH₂CH₂CH₂ H/HPyrimidin-2-yl C(CH₃)₂CH₂CH₂CH₂ H/H Pyrimidin-5-yl CH₂C(CH₃)₂CH₂CH₂ H/HPyridin-2-yl CH₂CH₂C(CH₃)₂CH₂ H/H Pyridin-3-yl CH₂CH₂CH₂CH₂ H/HPyridin-4-yl NHCH₂CH₂CH₂ Me/H Thiophen-2-yl NMeCH₂CH₂CH₂ H/HThiophen-3-yl OCH₂CH₂O H/H Thiophen-3-yl OCH₂CH₂O H/H5-Hydroxypyridin-3-yl C(CH₃)₂CH₂CH₂C(CH₃)₂ H/H 5-Methoxypyridin-3-ylCH₂CH₂CH₂CH₂ F/H 5-Aminopyridin-3-yl CH₂CH₂CH₂CH₂ Me/Me5-Chloropyridin-3-yl CH₂CH₂CH₂CH₂ Pr/H 6-Chloropyridin-3-yl

TABLE 16 A^(B)-B^(B)-D^(B)-E^(B) R^(24B)/R^(25B) T^(OB) CH₂CH₂CH₂CH₂Pr/H 6-Chloropyridin-3-yl CH₂CH₂CH₂CH₂ H/H 1H-Indazol-6-ylC(CH₃)₂CH₂CH₂CH₂ H/H 1H-Indazol-5-yl CH₂C(CH₃)₂CH₂CH₂ H/H1H-Indazol-4-yl CH₂CH₂C(CH₃)₂CH₂ H/H 1H-Benzotriazol-6-ylC(CH₃)₂CH₂CH₂CH₂ H/H 1H-Benzotriazol-4-yl CH₂CH₂CH₂CH₂ H/H1H-Benzimidazol-6-yl CH₂C(CH₃)₂CH₂CH₂ H/H 1H-Indazol-4-ylCH₂CH₂C(CH₃)₂CH₂ H/H 1H-Indol-6-yl C(CH₃)₂CH₂CH₂CH₂ H/H 1H-Indol-5-ylC(CH₃)₂CH₂CH₂CH₂ H/H 1H-Indol-4-yl CH₂C(CH₃)₂CH₂CH₂ H/HBenzisoxazol-6-yl C(CH₃)₂CH₂CH₂CH₂ H/H 1H-Benzimidazol-5-yl

TABLE 17 A^(B)-B^(B)-D^(B)-E^(B) R^(24B)/R^(25B) T^(OB) C(CH₃)₂CH₂CH₂CH₂H/H 1H-Benzimidazol-6-yl CH₂C(CH₃)₂CH₂CH₂ H/H 2-(Trifluoromethyl)-1H-benzimidazol-5-yl CH₂CH₂CH₂CH₂ H/H Quinolin-5-yl C(CH₃)₂CH₂CH₂CH₂ H/HQuinolin-8-yl

<Representative Compound B-400>

wherein A^(B)-B^(B)-D^(B), R^(23B), R^(24B), R^(25B), and R^(26B) are asdescribed in Tables 18 to 20.

TABLE 18 A^(B)-E^(B)-D^(B) R^(23B) R^(24B)/R^(25B) R^(26B) CH₂CH₂CH₂ HH/H 3-CN CH₂CH₂CH₂ H H/H 3-OH CH₂CH₂CH₂ H H/H 3-CO₂H CH₂CH₂CH₂ H H/H3-CONH₂ OCH₂O H H/H 3,4-OMe OCH₂O Me H/H 3,4-OMe OCH₂O Et H/H 3-OH, 4-FOCH₂O H H/H 3-NH₂ CH₂CH₂CH₂ H H/H 3-NHMe CH₂CH₂CH₂ H H/H 3-CF₃ CH₂CH₂CH₂H H/H 3-NHCH₂CF₃ CH₂CH₂CH₂ Me H/H 2-OH, 3-OH OCH₂O Et H/H 3,4,5-Me

TABLE 19 A^(B)-B^(B)-D^(B) R^(23B) R^(24B)/R^(25B) R^(26B) OCH₂O H Me/H4-OH OCH₂O H Me/Me 4-NH₂ OCH₂O H Pr/H 4-NO₂ CH₂CH₂CH₂ H H/H 4-CNCH₂CH₂CH₂ Me CF₃/H 4-Ph CH₂CH₂CH₂ Et H/H 4-CH₂OH OCH₂O H H/H 3-CH₂OHCH₂CH₂CH₂ H H/H 3-Ac CH₂CH₂CH₂ H H/H 3,5-OMe CH₂CH₂CH₂ H H/H 3-OH, 4-NH₂OCH₂O Me H/H 3-CH₂NH₂ CH₂CH₂CH₂ Et H/H 3-SO₂CH₃ CH₂CH₂CH₂ H Me/H 3-iPrCH₂CH₂CH₂ H Me/H 3-NMe₂ OCH₂O H Me/H 3-Ac CH₂CH₂CH₂ H Pr/H 3,4-NH₂

TABLE 20 A^(B)-B^(B)-D^(B) R^(23B) R^(24B)/R^(25B) R^(26B) CH₂CH₂CH₂ HH/H NHMe CH₂CH₂CH₂ Et H/H 3-NHCH₂CF₃ OCH₂O H H/H 3-NHAc CH₂CH₂CH₂ H H/H3-SO₂Me CH₂CH₂CH₂ H H/H 4-Me CH₂CH₂CH₂ H H/H 4-iPr OCH₂O Me H/H 3-PhCH₂CH₂CH₂ Et H/H 3-F, 4-OH CH₂CH₂CH₂ Ac H/H 3-F, 4-OMe

<Representative Compound B-500>

wherein A^(B)-B^(B)-D^(B), R^(24B), R^(25B), R^(26B), and R^(27B) are asdescribed in Tables 21 to 23; and the “Position” in the tables indicatesa R^(26B) substitution position.

TABLE 21 A^(B)-B^(B)-D^(B) R^(24B)/R^(25B) Position R^(26B) R^(27B)CH₂CH₂CH₂ H/H 3 1H-Tetrazol-5-yl H CH₂CH₂CH₂ H/H 4 1H-Tetrazol-5-yl HCH₂CH₂CH₂ H/H 3 1H-Tetrazol-1-yl 4-F CH₂CH₂CH₂ H/H 3 2-Methyl-2H- Htetrazol-5-yl OCH₂O H/H 3 1,2,3-Triazol-5-yl 2-F OCH₂O H/H 31,2,4-Triazol-3-yl H OCH₂O H/H 3 5-(Trifluoromethyl)- H1,2,4-triazol-3-yl OCH₂O H/H 4 1H-Imidazol-1-yl H CH₂CH₂CH₂ H/H 41H-Imidazol-2-yl H CH₂CH₂CH₂ H/H 3 5-Cyano-1H-1,2,3- H triazol-4-ylCH₂CH₂CH₂ H/H 3 1-Methyl-1H- H tetrazol-5-yl CH₂CH₂CH₂ Me/H 3Pyrazol-3-yl 4-OH

TABLE 22 A^(B)-B^(B)-D^(B) R^(24B)/R^(25B) Position R^(26B) R^(27B)OCH₂O Me/Me 3 Pyrazol-4-yl H OCH₂O H/H 3 5-Oxo-1,2,4-oxadiazol-3-yl4-NH₂ OCH₂O CF₃/H 3 1,2,4-Oxadiazol-3-yl H CH₂CH₂CH₂ H/H 31,3,4-Oxadiazol-2-yl 4-F CH₂CH₂CH₂ H/H 4 Pyrrol-1-yl 3-F CH₂CH₂CH₂ H/H 4Pyrrolidin-2-yl H OCH₂O H/H 2 1,3-Oxazol-5-yl H CH₂CH₂CH₂ H/H 31,3-Thiazol-5-yl H CH₂CH₂CH₂ H/H 3 5-(Trifluoromethyl)-1H- Himidazol-2-yl CH₂CH₂CH₂ H/H 3 5-Chloro-1H-imidazol-2-yl 4-OH OCH₂O Me/H4 5-Methyl-1H-imidazol-2-yl 4-NH₂ CH₂CH₂CH₂ Me/H 45-Amino-1H-imidazol-2-yl 3-F

TABLE 23 A^(B)-B^(B)-D^(B) R^(24B)/R^(25B) Position R^(26B) R^(27B)CH₂CH₂CH₂ Me/H 3 2-Ethyl-2H-tetrazol-5-yl H CH₂CH₂CH₂ Pr/H 32-(2,2,2-Trifluoroethyl)-2H- 2,6-F tetrazol-5-yl OCH₂O H/H 31,3-Oxazol-2-yl H CH₂CH₂CH₂ H/H 3 1,3-Thiazol-2-yl H CH₂CH₂CH₂ H/H 43,5-Dimethylisoxazol-4-yl H CH₂CH₂CH₂ H/H 3 3-Methyl-1,2,4-oxadiazol- H5-yl

<Representative Compound B-600>

wherein A^(B)-B^(B)-D^(B), R^(24B), R^(25B), and T^(0B) are as describedin Tables 24 to 26.

TABLE 24 A^(B)-B^(B)-D^(B) R^(24B)/R^(25B) T^(OB) CH₂CH₂CH₂ H/HPyrimidin-2-yl CH₂CH₂CH₂ H/H Pyrimidin-5-yl CH₂CH₂CH₂ H/H Pyridin-2-ylCH₂CH₂CH₂ H/H Quinolin-2-yl CH₂CH₂CH₂ H/H Quinolin-3-yl CH₂CH₂CH₂ H/HPyridin-3-yl OCH₂O H/H Pyridin-4-yl OCH₂O Me/H Thiophen-2-yl OCH₂O H/HThiophen-3-yl OCH₂O H/H Thiophen-3-yl CH₂CH₂CH₂ H/H5-Hydroxypyridin-3-yl CH₂CH₂CH₂ H/H 5-Methoxypyridin-3-yl NHCH₂CH₂ F/H5-Aminopyridin-3-yl

TABLE 25 A^(B)-B^(B)-D^(B) R^(24B)/R^(25B) T^(OB) CH₂CH₂CH₂ Me/Me5-Chloropyridin-3-yl OCH₂O Pr/H 6-Chloropyridin-3-yl OCH₂O Pr/H6-Chloropyridin-3-yl OCH₂O H/H 1H-Indazol-6-yl OCH₂O H/H 1H-Indazol-5-ylCH₂CH₂CH₂ H/H 1H-Indazol-4-yl CH₂CH₂CH₂ H/H 1H-Benzotriazol-6-ylCH₂CH₂CH₂ H/H 1H-Benzotriazol-4-yl OCH₂O H/H 1H-Benzimidazol-6-ylCH₂CH₂CH₂ H/H 1H-Indazol-4-yl CH₂CH₂CH₂ H/H 1H-Indol-6-yl

TABLE 26 A^(B)-B^(B)-D^(B) R^(24B)/R^(25B) T^(OB) NHCH₂CH₂ H/H1H-Indol-5-yl OCH₂O H/H 1H-Indol-4-yl CH₂CH₂CH₂ H/H Benzisoxazol-6-ylCH₂CH₂CH₂ H/H 1H-Benzimidazol-5-yl CH₂CH₂CH₂ H/H 1H-Benzimidazol-6-ylOCH₂O H/H 2-Trifluoromethyl-1H- benzimidazol-5-yl CH₂CH₂CH₂ H/HQuinolin-5-yl CH₂CH₂CH₂ H/H Quinolin-8-yl

(C-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (CI):

wherein R^(1C) and R^(2C) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, an aralkyl group(the number of carbon atoms in an aryl moiety is from 6 to 10 and thenumber of carbon atoms in an alkylene moiety is from 1 to 3), a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a C₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, aC₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,

R^(3C) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 3),

R^(4C) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, an aralkyl group (the number of carbon atoms in an aryl moiety isfrom 6 to 10 and the number of carbon atoms in an alkylene moiety isfrom 1 to 3), a hydroxyl-substituted C₁₋₈ alkyl group, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₁₋₅ alkylamino group substituted with 1 to 5halogen atoms, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a C₂₋₈acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, an optionally substituted benzenesulfonylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoylgroup, a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈alkylsulfonyl group, a sulfamoyl group, an optionally substituted phenylgroup, or an optionally substituted heterocyclic ring group,

is condensed with a benzene ring at positions 1 and 2 and represents a5- to 8-membered ring optionally comprising, as a ring constituentelement, a heteroatom selected from N, S, or O, and

represents an aromatic ring selected from a benzene ring, a naphthalenering, a pyridine ring, a pyrimidine ring, a quinoline ring, an indolering, an indoline ring, a benzimidazole ring, an indazole ring, abenzisoxazole ring, or a benztriazole ring.

(C-2) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (CII):

wherein R^(11C) and R^(12C) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, an aralkyl group(the number of carbon atoms in an aryl moiety is from 6 to 10 and thenumber of carbon atoms in an alkylene moiety is from 1 to 3), a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a C₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, aC₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,

R^(13C) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 3),

R^(14C) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, an aralkyl group (the number of carbon atoms in an aryl moiety isfrom 6 to 10 and the number of carbon atoms in an alkylene moiety isfrom 1 to 3), a hydroxyl-substituted C₁₋₈ alkyl group, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₁₋₅ alkylamino group substituted with 1 to 5halogen atoms, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a C₂₋₈acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, an optionally substituted benzenesulfonylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoylgroup, a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈alkylsulfonyl group, a sulfamoyl group, an optionally substituted phenylgroup, or an optionally substituted heterocyclic ring group, and

represents a naphthalene ring, a tetrahydronaphthalene ring, or anindane ring.

Examples of the C₁₋₈ alkyl group of R^(1C), R^(2C), R^(3C), or R^(4C) ingeneral formula (CI) include a methyl, ethyl, propyl, isopropyl, butyl,i-butyl, t-butyl, pentyl, or hexyl group.

Examples of the C₂₋₈ alkenyl group of R^(1C), R^(2C), R^(3C), or R^(4C)include an allyl group.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsin R^(1C), R^(2C), R^(3C), or R^(4C) include a methyl, ethyl, propyl,isopropyl, butyl, or t-butyl group substituted with 1 to 3 halogen atomssuch as fluorine, chlorine, or bromine atoms, and preferably atrifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl, or2-fluoroethyl group.

Examples of the aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 3) of R^(1C), R^(2C), R^(3C), or R^(4C) include abenzyl group.

Examples of the C₁₋₈ alkoxy group of R^(1C), R^(2C), or R^(4C) include amethoxy, ethoxy, propoxy, isopropoxy, butoxy, i-butoxy, t-butoxy,pentyloxy, or hexyloxy group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsin R^(1C), R^(2C), or R^(4C) include a methoxy, ethoxy, propoxy,isopropoxy, butoxy, or t-butoxy group substituted with 1 to 3 halogenatoms such as fluorine, chlorine, or bromine atoms, and preferably atrifluoromethoxy, chloromethoxy, 2-chloroethoxy, 2-bromoethoxy, or2-fluoroethoxy group.

Examples of the halogen atom of R^(1C), R^(2C), or R^(4C) include afluorine, chlorine, or bromine atom.

Examples of the C₁₋₈ alkylamino group of R^(1C), R^(2C), or R^(4C)include a methylamino or ethylamino group.

Examples of the C₁₋₅ alkylamino group substituted with 1 to 5 halogenatoms in R^(4C) include a 2,2,2-trifluoroethylamino group.

Examples of the C₂₋₈ dialkylamino group of R^(1C), R^(2C), or R^(4C)include a dimethylamino or diethylamino group.

Examples of the C₂₋₈ acylamino group of R^(1C), R^(2C), or R^(4C)include an acetylamino group. Examples include a benzoylamino groupfurther optionally having a substituent (e.g., a C₁₋₈ alkyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen).

Examples of the C₂₋₈ acylamino group substituted with 1 to 3 halogenatoms in R^(1C), R^(2C), or R^(4C) include atrifluoromethylcarbonylamino group.

Examples of the C₁₋₈ alkylsulfonylamino group of R^(1C), R^(2C), orR^(4C) include a methylsulfonylamino group.

Examples of the C₂₋₈ acyl group of R^(1C), R^(2C), or R^(4C) include anacetyl group.

Examples of the alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8) of R^(1C), R^(2C), or R^(4C) include amethoxycarbonyl group or an ethoxycarbonyl group.

Examples of the C₁₋₈ alkylthio group of R^(1C), R^(2C), or R^(4C)include a methylthio group.

Examples of the C₁₋₈ alkylsulfinyl group of R^(1C), R^(2C), or R^(4C)include a methylsulfinyl group.

Examples of the C₁₋₈ alkylsulfonyl group of R^(1C), R^(2C), or R^(4C)include a methylsulfonyl group.

Examples of the hydroxyl-substituted C₁₋₈ alkyl group of R^(4C) includea hydroxymethyl group.

Examples of the optionally substituted benzenesulfonylamino group ofR^(4C) include a benzenesulfonylamino group and preferably ano-nitrobenzenesulfonylamino group optionally having a substituentselected from a C1-8 alkyl group (e.g., a methyl group, an ethyl group),a C1-8 alkoxy group (e.g., a methoxy group, an ethoxy group), a halogenatom (e.g., a fluorine atom, a chlorine atom), or a nitro group.

Examples of a preferable substituent of the optionally substitutedphenyl group of R^(4C) include a C₁₋₈ alkyl group such as a methyl orethyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atomssuch as a trifluoromethyl group, a halogen atom such as a fluorine atom,or a cyano group.

Examples of a preferable heterocyclic ring group in the optionallysubstituted heterocyclic ring group of R^(4C) include a tetrazolyl,triazolyl, pyridyl, imidazolyl, oxazolyl or thiazolyl group. Examplesfurther include an oxadiazole group.

Examples of a preferable substituent of the optionally substitutedheterocyclic ring of R^(4C) include a C₁₋₈ alkyl group such as a methylor ethyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atomssuch as a trifluoromethyl group, a halogen atom such as a fluorine atom,a cyano group, or oxo.

Examples of

include a naphthalene ring, a tetrahydronaphthalene ring, or an indanering.

In general formula (CI), R^(1C), R^(2C), or R^(4C) substituents, whichare the same or different, may be present, in a ring having the R^(1C),R^(2C), or R^(4C) substituents.

Regarding the above listed examples, for R^(1C), R^(2C), R^(3C), orR^(4C) in general formula (CI), comprising a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group, a C₁₋₈ alkoxy group substituted with1 to 3 halogen atoms, a halogen atom, an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 3), a hydroxyl-substituted C₁₋₈alkyl group, a halogen atom, a C₁₋₈ alkylamino group, a C₁₋₅ alkylaminosubstituted with 1 to 5 halogen atoms, a C₂₋₈ dialkylamino group, a C₂₋₈acylamino group, a C₂₋₈ acylamino group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkylsulfonylamino group, an optionally substitutedbenzenesulfonylamino group, a C₂₋₈ acyl group, an alkoxycarbonyl group(the number of carbon atoms in an alkoxy moiety is from 1 to 8), a C₁₋₈alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group,an optionally substituted phenyl group, or an optionally substitutedheterocyclic ring group, the same applies to R^(11C), R^(12C), R^(13C),or R^(14C) in general formula (CII).

Regarding the optionally substituted heterocyclic ring group of R^(14C)in general formula (CII), examples of the substituent include a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a C₁₋₈ alkylamino group, and a C₂₋₈ dialkylaminogroup, examples of which are included in those listed for R^(1C) toR^(4C) in general formula (CI).

Examples of

include a naphthalene ring, a tetrahydronaphthalene ring, or an indanering.

In general formula (CII), R^(11C), R^(12C), or R^(14C) substituents,which are the same or different, may be present, in a benzene ringhaving the R^(11C), R^(12C), or R^(14C) substituents.

The following compounds are preferable as compounds included in generalformula (CI).

(C-1-1) A compound described in (C-1), wherein R^(1C) and R^(2C) are thesame or different and are a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, or an amino group.

(C-1-2) A compound described in (C-1) or (C-1-1), wherein R^(3C) is ahydrogen atom or a C₁₋₈ alkyl group.

(C-1-3) A compound described in (C-1) or (C-1-1) or (C-1-2), whereinR^(4C) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C₁₋₈alkyl group, a halogen atom, a hydroxyl group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₁₋₈alkylsulfonylamino group, an optionally substituted benzenesulfonylaminogroup, an optionally substituted phenyl group, or an optionallysubstituted heterocyclic ring group.

(C-1-4) A compound described in (C-1) or any of (C-1-1) to (C-1-3),wherein R^(4C) is a 5- or 6-membered heterocyclic ring comprising 1 to 4atoms of nitrogen as a ring constituent element.

(C-1-5) A compound described in (C-1) or any of (C-1-1) to (C-1-4),wherein R^(4C) is a tetrazolyl, triazolyl, pyridyl, imidazolyl,oxazolyl, or thiazolyl group optionally having a substituent selectedfrom a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group.

(C-1-6) A compound described in (C-1) or any of (C-1-1) to (C-1-5),wherein R^(4C) is tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, or imidazole optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, a cyano group, an oxo group, or athioxo group.

(C-1-7) A compound described in (C-1) or any of (C-1-1) to (C-1-6),wherein R^(4C) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(C-1-8) A compound described in (C-1) or any of (C-1-1) to (C-1-7),wherein R^(4C) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(C-1-9) A compound described in (C-1) or any of (C-1-1) to (C-1-8),wherein R^(4C) is tetrazole.

(C-1-10) A compound described in (C-1) or any of (C-1-1) to (C-1-9),wherein R^(4C) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a cyano group, an amino group, a C₁₋₈ alkylamino group,a C₂₋₈ dialkylamino group, or a benzenesulfonylamino group optionallyhaving a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a halogen atom, or a nitro group.

(C-1-11)

A compound described in (C-1) or any of (C-1-1) to (C-1-10), wherein

is a naphthalene ring, a tetrahydronaphthalene ring, or an indane ring.

(C-1-12)

A compound described in (C-1) or any of (C-1-1) to (C-1-11), wherein

is a benzene ring or an indole ring.

The following compounds are preferable as compounds included in generalformula (CII).

(C-2-1) A compound described in (C-2), wherein R^(11C) and R^(12C) arethe same or different and are a hydrogen atom, a C₁₋₈ alkyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, or anamino group.

(C-2-2) A compound described in (C-2) or (C-2-1), wherein R^(13C) is ahydrogen atom or a C₁₋₈ alkyl group.

(C-2-3) A compound described in (C-2) or (C-2-1) or (C-2-2), whereinR^(14C) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C₁₋₈alkyl group, a halogen atom, a hydroxyl group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₁₋₈alkylsulfonylamino group, an optionally substituted benzenesulfonylaminogroup, an optionally substituted phenyl group, or an optionallysubstituted heterocyclic ring group.

(C-2-4) A compound described in (C-2) or any of (C-2-1) to (C-2-3),wherein R^(14C) is a 5- or 6-membered heterocyclic ring comprising 1 to4 atoms of nitrogen as a ring constituent element.

(C-2-5) A compound described in (C-2) or any of (C-2-1) to (C-2-4),wherein R^(14C) is a tetrazolyl, triazolyl, pyridyl, imidazolyl,oxazolyl, or thiazolyl group optionally having a substituent selectedfrom a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group.

(C-2-6) A compound described in (C-2) or any of (C-2-1) to (C-2-5),wherein R^(14C) is tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, or imidazole optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, a cyano group, an oxo group, or athioxo group.

(C-2-7) A compound described in (C-2) or any of (C-2-1) to (C-2-6),wherein R^(14C) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(C-2-8) A compound described in (C-2) or any of (C-2-1) to (C-2-7),wherein R^(14C) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(C-2-9) A compound described in (C-2) or any of (C-2-1) to (C-2-8),wherein R^(14C) is tetrazole.

(C-2-10) A compound described in (C-2) or any of (C-2-1) to (C-2-9),wherein R^(14C) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a cyano group, an amino group, a C₁₋₈ alkylamino group,a C₂₋₈ dialkylamino group, or a benzenesulfonylamino group optionallyhaving a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a halogen atom, or a nitro group.

(C-2-11)

A compound described in (C-2) or any of (C-2-1) to (C-2-10), wherein

is a naphthalene ring.

Examples further include the following compounds.

(C-2-12) A compound described in (C-2), wherein R^(11C) and R^(12C) arethe same or different and are a hydrogen atom, a C₁₋₈ alkyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, or anamino group.

(C-2-13) A compound described in (C-2) or (C-2-12), wherein R^(13C) is ahydrogen atom or a C₁₋₈ alkyl group.

(C-2-14)

A compound described in (C-2) or any of (C-2-12) or (C-2-13), wherein

is a naphthalene ring.

(C-2-15) A compound described in (C-2) or any of (C-2-12) to (C-2-14),wherein R^(14C) is NHSO₂R^(C) (where R^(C) represents an optionallysubstituted aryl or heterocyclic ring group).

(C-2-16) A compound described in (C-2-15), wherein R^(C) is phenyl,naphthyl, quinolyl, pyridyl, or thienyl optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a hydroxyl group, an amino group,a nitro group, nitro, or halogen.

The following shows representative compounds included in general formula(CI).

<Representative Compound C-100>

wherein R^(1C), R^(3C), and R^(4C) are as described in Tables 27 to 29.

TABLE 27 R^(1C) R^(3C) R^(4C) H H 3-OH H H 3-OMe H H 4-OH H H 4-OMe H H2-OH H H 2-OMe H H 2,3-OH H H 3-OH, 4-F H H 3,4-OH H H 3,4-OMe H H3,4,5-OMe H H 3-CN

TABLE 28 R^(1C) R^(3C) R^(4C) H H 4-CN H H 3-CO₂H H H 3-CO₂Me H H 3-Br HH 3-F H H 4-Me H H S-NH₂ H H 3-NHSO₂Ph H H 3-NHSO₂(2-NO₂)Ph H H4-NHSO₂Ph H Me 4-NHSO₂(2-NO₂)Ph H Et 3-NHEt H H 3-CH₂OH H H 4-CH₂OH

TABLE 29 R^(1C) R^(3C) R^(4C) H H 3-CF₃ H H 3-Ph H H 3-N(Me)₂ H H 3,5-OHH H 4-OAc H H 2-Me 9-Me H 3-NH₂ 9-Cl H 3-NH₂ 8-Me H 3-NH₂ 8-Cl H 3-NH₂

<Representative Compound C-200>

wherein R^(1C), R^(3C), R^(4C), and R^(5C) are as described in Tables 30to 32; and the “R^(4C) position” in the tables indicates a R^(4C)substitution position.

TABLE 30 R^(4C) R^(1C) R^(3C) Position R^(4C) R^(5C) H H 31H-Tetrazol-5-yl H H H 4 1H-Tetrazol-5-yl H 8-Me H 3 1H-Tetrazol-5-yl H8-Cl H 3 1H-Tetrazol-5-yl H H H 3 1H-Tetrazol-5-yl 4-F H H 31H-Tetrazol-5-yl 4-Me H H 3 1H-Tetrazol-5-yl 5-Br H H 3 1H-Tetrazol-5-yl6-Me H H 3 1H-Tetrazol-5-yl 6-Cl H H 3 (5-Thioxo-1,2,4-oxadiazol)-3-yl HH H 3 (5-Oxo-1,2,4-oxadiazol)-3-yl H H H 3(5-Cyano-1H-1,2,3-triazol)-4-yl H

TABLE 31 R^(4C) R^(1C) R^(3C) Position R^(4C) R^(5C) H H 31H-Tetrazol-5-yl 6-OH H H 3 (2-Methyl-2H-tetrazol)-5-yl H H Me 3(2-Methyl-2H-tetrazol)-5-yl H H Et 3 (2-Ethyl-2H-tetrazol)-5-yl H H H 3(1-Methyl-1H-tetrazol)-5-yl H H H 3 4-Methyl-(5-thioxo-1,2,4- Hoxadiazol)-3-yl H H 3 1-Methyl-1H-imidazol-2-yl H H H 31-Methyl-1H-imidazol-4-yl H H H 3 1,3-Oxazol-2-yl H H H 31,3-Thiazol-2-yl H H H 3 Pyrrol-2-yl H H H 3 Thiophen-2-yl H H H 31-H-Imidazol-2-yl H H H 3 1-H-Imidazol-4-yl H

TABLE 32 R^(4C) R^(1C) R^(3C) Position R^(4C) R^(5C) H H 3 Pyrazol-4-ylH H H 3 5-(Chloro)-1H-imidazol-2-yl H H H 35-(Trifluoromethyl)-1H-imidazol-2-yl H H H 3 (1,2,3-Triazol)-4-yl H H H3 (1,2,3-Triazol)-3-yl H H H 3 3-Methyl-(1,2,4-oxadiazol)-5-yl H H H 33,5-Dimethylisoxazol-4-yl H H H 3 1-Tetrazol-1-yl H H H 3 Phenyl H H H 3Pyridin-3-yl H H H 3 Pyrimidin-5-yl H H H 3 2-Aminopyridin-5-yl H

<Representative Compound C-300>

wherein R^(1C), R^(3C), and T^(C) are as described in Tables 33 and 34.

TABLE 33 R^(1C) R^(3C) T^(C) H H 1H-Indol-6-yl H H 1H-Indolin-6-yl H H1H-Indol-4-yl H H 1H-Indazol-6-yl H Me 1H-Indazol-6-yl H Et1H-Indazol-6-yl 8-Me H 1H-Indazol-6-yl 8-Cl H 1H-Indazol-6-yl H H1H-Indazol-4-yl H H 1H-Benzimidazol-6-yl H H2-(Trifluoromethyl)-1H-benzimidazol-6-yl H H 1H-Benzotriazol-6-yl

TABLE 34 R^(1C) R^(3C) T^(C) H H 3-Methylbenzisoxazol-6-yl H HPyridin-4-yl H H 3-Methoxypyridin-5-yl H H 3-Hydroxypyridin-5-yl H HPyridin-3-yl H H 7-Hydroxyquinolin-3-yl H H Pyrimidin-2-yl H HThiophen-2-yl H H Pyridin-2-yl H H 4-Methylpyridin-2-yl H H2-Bromopyridin-5-yl

<Representative Compound C-400>

wherein A^(C)-B^(C)-D^(C)-E^(C), R^(3C), and R^(4C) are as described inTables 35 to 37.

TABLE 35 A^(C)-B^(C)-D^(C)-E^(C) R^(3C) R^(4C) CH₂CH₂CH₂CH₂ H 3-OHCH₂CH₂CH₂CH₂ H 3-OMe CH₂CH₂CH₂CH₂ H 4-OH CH₂CH₂CH₂CH₂ H 4-OMeCH₂CH₂CH₂CH₂ H 2-OH CH₂CH₂CH₂CH₂ H 2-OMe CH₂CH₂CH₂CH₂ H 2,3-OHCH₂CH₂CH₂CH₂ H 3-OH,4-F CH₂CH₂CH₂CH₂ H 3,4-OH CH₂CH₂CH₂CH₂ H 3,4-OMeCH₂CH₂CH₂CH₂ H 3,4,5-OMe CH₂CH₂CH₂CH₂ H 3-CN

TABLE 36 A^(C)-B^(C)-D^(C)-E^(C) R^(3C) R^(4C) CH₂NHCH₂CH₂ H 4-CNCH₂CH₂CH₂CH₂ H 3-CO₂H CH₂NHCH₂CH₂ H 3-CO₂Me CH₂CH₂CH₂CH₂ H 3-BrCH₂CH₂NHCH₂ H 3-F CH₂CH₂OCH₂ H 4-Me CH₂CH₂CH₂CH₂ H 3-NH₂ CH₂CH₂CH₂CH₂ H3-NHSO₂Ph CH₂CH₂CH₂CH₂ H 3-NHSO₂(2-NO₂)Ph CH₂CH₂CH₂CH₂ H 4-NHSO₂PhCH₂CH₂CH₂CH₂ Me 4-NHSO₂(2-NO₂)Ph CH₂CH₂CH₂CH₂ Et 3-NHEt

TABLE 37 A^(C)-B^(C)-D^(C)-E^(C) R^(3C) R^(4C) CH₂CH₂CH₂CH₂ H 3-CH₂OHCH₂CH₂CH₂CH₂ H 3-NHSO₂CH₃ CH₂CH₂CH₂CH₂ H S-CF₃ CH₂CH₂CH₂CH₂ H 3-PhCH₂CH₂CH₂CH₂ H 3-N(Me)₂ CH₂CH₂CH₂CH₂ H 3,5-OH CH₂CH₂CH₂CH₂ H 4-OAcCH₂CH₂CH₂CH₂ H 2-Me CH₂CH(Me)CH₂CH₂ H 3-NH₂

<Representative Compound C-500>

wherein A^(C)-B^(C)-D^(C)-E^(C), R^(3C), R^(4C), and R^(5C) are asdescribed in Tables 38 to 40; and the “R^(4C) position” in the tablesindicates a R^(4C) substitution position.

TABLE 38 R^(4C) A^(C)-B^(C)-D^(C)-E^(C) R^(3C) Position R^(4C) R^(5C)CH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl H CH₂CH₂CH₂CH₂ H 4 1H-Tetrazol-5-yl HCH₂NHCH₂CH₂ H 3 1H-Tetrazol-5-yl H CH₂CH₂OCH₂ H 3 1H-Tetrazol-5-yl 4-FCH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 4-Me CH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl5-Br CH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 6-Me CH₂CH₂CH₂CH₂ H 31H-Tetrazol-5-yl 6-Cl CH₂CH₂CH₂CH₂ H 3 (5-Thioxo-1,2,4-oxadiazol)-3-yl HCH₂CH₂CH₂CH₂ H 4 (5-Oxo-1,2,4-oxadiazol)-3-yl H

TABLE 39 R^(4C) A^(C)-B^(C)-D^(C)-E^(C) R^(3C) Position R^(4C) R^(5C)CH₂CH₂CH₂CH₂ H 3 (5-Cyano-1H-1,2,3-triazol)-4-yl H CH₂CH₂CH₂CH₂ H 31H-Tetrazol-5-yl 6-OH CH₂CH₂CH₂CH₂ H 3 (2-Methyl-2H-tetrazol)-5-yl HCH₂CH₂CH₂CH₂ Me 3 (2-Methyl-2H-tetrazol)-5-yl H CH₂CH₂CH₂CH₂ Et 3(2-Ethyl-2H-tetrazol)-5-yl H CH₂NHCH₂CH₂ H 3 (1-Methyl-1H-tetrazol)-5-ylH CH₂CH₂CH₂CH₂ H 3 4-Methyl-(5-thioxo-1,2,4- H oxadiazol)-3-ylCH₂CH₂CH₂CH₂ H 3 1-Methyl-1H-imidazol-2-yl H CH₂CH₂CH₂CH₂ H 31-Methyl-1H-imidazol-4-yl H CH₂CH₂CH₂CH₂ H 3 1,3-Oxazol-2-yl HCH₂CH₂CH₂CH₂ H 3 1,3-Thiazol-2-yl H CH₂CH₂CH₂CH₂ H 3 Pyrrol-2-yl HCH₂CH₂CH₂CH₂ H 3 Thiophen-2-yl H

TABLE 40 R^(4C) A^(C)-B^(C)-D^(C)-E^(C) R^(3C) Position R^(4C) R^(5C)CH₂CH₂CH₂CH₂ H 3 1-H-Imidazol-2-yl H CH₂CH₂CH₂CH₂ H 3 1-H-Imidazol-4-ylH CH₂CH₂CH₂CH₂ H 4 Pyrazol-4-yl H CH₂CH₂CH₂CH₂ H 35-(Chloro)-1H-imidazol-2-yl H CH₂CH₂CH₂CH₂ H 3 5-(Trifluoromethyl)-1H- Himidazol-2-yl CH₂CH₂CH₂CH₂ H 3 (1,2,3-Triazol)-4-yl H CH₂CH₂CH₂CH₂ H 3(1,2,4-Triazol)-3-yl H CH₂CH₂CH₂CH₂ H 3 3-Methyl-(1,2,4-oxadiazol)-5-ylH CH₂CH₂CH₂CH₂ H 4 3,5-Dimethylisoxazol-4-yl H CH₂CH₂CH₂CH₂ H 31-Tetrazol-1-yl H CH₂CH(Me)CH₂CH₂ H 3 Phenyl H CH₂CH₂CH(Me)CH₂ H 3Pyrimidin-5-yl H

<Representative Compound C-600>

wherein A^(C)-B^(C)-D^(C)-E^(C), R^(3C), and T^(C) are as described inTables 41 and 42.

TABLE 41 A^(C)-B^(C)-D^(C)-E^(C) R^(3C) T^(C) CH₂CH₂CH₂CH₂ H1H-Indol-6-yl CH₂CH₂CH₂CH₂ H 1H-Indolin-6-yl CH₂CH₂CH₂CH₂ H1H-Indol-4-yl CH₂CH₂CH₂CH₂ H 1H-Indazol-6-yl CH₂CH₂CH₂CH₂ Me1H-Indazol-6-yl CH₂CH₂CH₂CH₂ Et 1H-Indazol-6-yl CH₂CH₂CH₂CH₂ H1H-Indazol-4-yl CH₂CH₂CH₂CH₂ H 1H-Benzimidazol-6-yl CH₂CH₂CH₂CH₂ H2-(Trifluoromethyl)-1H-benzimidazol-6-yl CH₂CH₂CH₂CH₂ H1H-Benzotriazol-6-yl CH₂CH₂CH₂CH₂ H 3-Methylbenzisoxazol-6-yl

TABLE 42 A^(C)-B^(C)-D^(C)-E^(C) R^(3C) T^(C) CH₂CH₂CH₂CH₂ HPyridin-4-yl CH₂CH₂CH₂CH₂ H 3-Methoxypyridin-5-yl CH₂CH₂CH₂CH₂ H3-Hydroxypyridin-5-yl CH₂CH₂CH₂CH₂ H Pyridin-3-yl CH₂CH₂CH₂CH₂ H7-Hydroxyquinolin-3-yl CH₂CH₂CH₂CH₂ H Pyrimidin-2-yl CH₂CH₂CH₂CH₂ HThiophen-2-yl CH₂CH₂CH₂CH₂ H Pyridin-2-yl CH₂CH₂CH₂CH₂ H4-Methylpyridin-2-yl CH₂CH₂CH₂CH₂ H 2-Bromopyridin-5-yl CH₂CH(Me)CH₂CH₂H 1H-Indol-6-yl CH₂CH(Me)CH₂CH₂ H 1H-Indol-5-yl CH₂CH(Me)CH₂CH₂ H1H-Indol-4-yl

<Representative Compound C-700>

wherein A^(C)-B^(C)-D^(C), R^(3C), and R^(4C) are as described in Tables43 to 45.

TABLE 43 A^(C)-B^(C)-D^(C) R^(3C) R^(4C) CH₂CH₂CH₂ H 3-OH CH₂CH₂CH₂ H3-OMe CH₂CH₂CH₂ H 4-OH CH₂CH₂CH₂ H 4-OMe OCH₂O H 2,3-OH CH₂CH₂CH₂ H3,4-OH NHCH₂CH₂ H 3,4,5-OMe CH₂CH₂CH₂ H 3-CN

TABLE 44 A^(C)-B^(C)-D^(C) R^(3C) R^(4C) CH₂CH₂CH₂ H 3-CO₂H OCH₂O H 3-BrCH₂CH₂CH₂ H 4-Me CH₂NHCH₂ H 3-NHSO₂Ph CH₂CH₂CH₂ H 3-NHSO₂(2-NO₂)PhCH₂CH₂CH₂ H 4NHSO₂Ph CH₂CH₂CH₂ Me 4-NHSO₂(2-NO₂)Ph CH₂CH₂CH₂ Et 3-NHEt

TABLE 45 A^(C)-B^(C)-D^(C) R^(3C) R^(4C) CH₂CH₂CH₂ H 3-NHSO₂CH₃CH₂CH₂CH₂ H 3-Ph CH₂CH₂CH₂ H S—N(Me)₂ CH₂CH₂NH H 2-Me CH₂CH(Me)CH₂ H3-NH₂ CH₂CH(Me)CH₂ H 4-NH₂

<Representative Compound C-800>

wherein A^(C)-B^(C)-D^(C), R^(3C), R^(4C), and R^(5C) are as describedin Tables 46 to 48; and the “R^(4C) position” in the tables indicates aR^(4C) substitution position.

TABLE 46 R^(4C) A^(C)-B^(C)-D^(C) R^(3C) Position R^(4C) R^(5C)CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl H OCH₂O H 4 1H-Tetrazol-5-yl HCH₂CH(Me)CH₂ H 3 1H-Tetrazol-5-yl H CH₂CH(Me)CH₂ H 4 1H-Tetrazol-5-yl HCH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 4-F CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 4-MeCH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 5-Br CH₂NHCH₂ H 3 1H-Tetrazol-5-yl 6-MeCH₂CH₂CH₂ H 3 (5-Thioxo-1,2,4-oxadiazol)-3-yl H

TABLE 47 R^(4C) A^(C)-B^(C)-D^(C) R^(3C) Position R^(4C) R^(5C)CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 6-OH CH₂CH₂CH₂ H 3(2-Methyl-2H-tetrazol)-5-yl H CH₂CH₂CH₂ Me 3 (2-Methyl-2H-tetrazol)-5-ylH CH₂CH₂CH₂ Et 3 (2-Ethyl-2H-tetrazol)-5-yl H CH₂CH₂CH₂ H 34-Methyl-(5-thioxo-1,2,4-oxadiazol)-3-yl H CH₂CH₂CH₂ H 31-Methyl-1H-imidazol-2-yl H CH₂CH₂CH₂ H 3 1,3-Oxazol-2-yl H CH₂CH₂CH₂ H3 1,3-Thiazol-2-yl H CH₂CH₂CH₂ H 3 Thiophen-2-yl H

TABLE 48 R^(4C) A^(C)-B^(C)-D^(C) R^(3C) Position R^(4C) R^(5C)CH₂CH₂CH₂ H 3 1-H-Imidazol-4-yl H CH₂CH₂CH₂ H 3 Pyrazol-4-yl H CH₂CH₂CH₂H 3 5-(Chloro)-1H-imidazol-2-yl H CH₂CH₂CH₂ H 3 (1,2,4-Triazol)-3-yl HCH₂CH₂CH₂ H 3 1-Tetrazol-1-yl H OCH₂O H 3 Phenyl H CH₂CH₂CH₂ H 3Pyridin-3-yl H NHCH₂CH₂ H 3 Pyrimidin-5-yl H

<Representative Compound C-900>

wherein A^(C)-B^(C)-D^(C), R^(3C), and T^(C) are as described in Tables49 and 50.

TABLE 49 A^(C)-B^(C)-D^(C) R^(3C) T^(C) CH₂CH₂CH₂ H 1H-Indol-6-yl OCH₂OH 1H-Indolin-6-yl CH₂CH₂CH₂ Me 1H-Indazol-6-yl CH₂CH₂CH₂ Et1H-Indazol-6-yl OH₂CH₂CH₂ H 1H-Indazol-4-yl CH₂NHCH₂ H1H-Benzotriazol-6-yl CH₂CH₂CH₂ H 3-Methylbenzisoxazol-6-yl

TABLE 50 A^(C)-B^(C)-D^(C) R^(3C) T^(C) CH₂CH₂CH₂ H Pyridin-4-ylCH₂CH₂CH₂ H Thiophen-2-yl CH₂NHCH₂ H 4-Methylpyridin-2-yl CH₂CH(Me)CH₂ H1H-Indol-6-yl

(D-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (DI):

wherein R^(1D) and R^(2D) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, an aralkyl group(the number of carbon atoms in an aryl moiety is from 6 to 10 and thenumber of carbon atoms in an alkylene moiety is from 1 to 3), a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a C₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, aC₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,

R^(3D) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 3),

R^(4D) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, an aralkyl group (the number of carbon atoms in an aryl moiety isfrom 6 to 10 and the number of carbon atoms in an alkylene moiety isfrom 1 to 3), a hydroxyl-substituted C₁₋₈ alkyl group, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₁₋₈ alkylamino group substituted with 1 to 5halogen atoms, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a C₂₋₈acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, an optionally substituted benzenesulfonylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoylgroup, a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈alkylsulfonyl group, a sulfamoyl group, an optionally substituted phenylgroup, or an optionally substituted heterocyclic ring group, and

is condensed with a benzene ring at positions 1 and 2 and represents a5- to 8-membered ring optionally comprising 1 or 2 atoms of nitrogen asa ring constituent element, and

represents an aromatic ring selected from a benzene ring, a naphthalenering, a pyridine ring, a pyrimidine ring, a quinoline ring, an indolering, an indoline ring, a benzimidazole ring, a pyrazole ring, anindazole ring, a benzisoxazole ring, or a benzotriazole ring.

(D-2) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (DII):

wherein R^(11D) and R^(12D) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, an aralkyl group(the number of carbon atoms in an aryl moiety is from 6 to 10 and thenumber of carbon atoms in an alkylene moiety is from 1 to 3), a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a C₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, aC₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,

R^(13D) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 3),

R^(14D) represents a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 3), a hydroxyl-substituted C₁₋₈alkyl group, a hydroxyl group, a nitro group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, a C₁₋₅ alkylamino group substituted with1 to 5 halogen atoms, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group,a C₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, an optionally substituted benzenesulfonylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoylgroup, a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈alkylsulfonyl group, a sulfamoyl group, an optionally substituted phenylgroup, or an optionally substituted heterocyclic ring group, and

represents a naphthalene ring, a tetrahydronaphthalene ring, or anindane ring.

Examples of the C₁₋₈ alkyl group of R^(1D), R^(2D), R^(3D), or R^(4D) ingeneral formula (DI) include a methyl, ethyl, propyl, isopropyl, butyl,i-butyl, t-butyl, pentyl, or hexyl group.

Examples of the C₂₋₈ alkenyl group of R^(lD), R^(2D), R^(3D), or R^(4D)include an allyl group.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsin R^(1D), R^(2D), R^(3D), or R^(4D) include a methyl, ethyl, propyl,isopropyl, butyl, or t-butyl group substituted with 1 to 3 halogen atomssuch as fluorine, chlorine, or bromine atoms, and preferably atrifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl, or2-fluoroethyl group.

Examples of the aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 3) of R^(1D), R^(2D), R^(3D), or R^(4D) include abenzyl group.

Examples of the C₁₋₈ alkoxy group of R^(1D), R^(2D), or R^(4D) include amethoxy, ethoxy, propoxy, isopropoxy, butoxy, i-butoxy, t-butoxy,pentyloxy, or hexyloxy group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsin R^(1D), R^(2D), or R^(4D) include a methoxy, ethoxy, propoxy,isopropoxy, butoxy, or t-butoxy group substituted with 1 to 3 halogenatoms such as fluorine, chlorine, or bromine atoms, and preferably atrifluoromethoxy, chloromethoxy, 2-chloroethoxy, 2-bromoethoxy, or2-fluoroethoxy group.

Examples of the halogen atom of R^(1D), R^(2D), or R^(4D) include afluorine, chlorine, or bromine atom.

Examples of the C₁₋₈ alkylamino group of R^(1D), R^(2D), or R^(4D)include a methylamino or ethylamino group.

Examples of the C₁₋₅ alkylamino group substituted with 1 to 5 halogenatoms in R^(4D) include a 2,2,2-trifluoroethylamino group.

Examples of the C₂₋₈ dialkylamino group of R^(1D), R^(2D), or R^(4D)include a dimethylamino or diethylamino group.

Examples of the C₂₋₈ acylamino group of R^(1D), R^(2D), or R^(4D)include an acetylamino group.

Examples of the C₂₋₈ acylamino group substituted with 1 to 3 halogenatoms in R^(1D), R^(2D), or R^(4D) include atrifluoromethylcarbonylamino group.

Examples of the C₁₋₈ alkylsulfonylamino group of R^(1D), R^(2D), orR^(4D) include a methylsulfonylamino group.

Examples of the C₂₋₈ acyl group of R^(1D), R^(2D), or R^(4D) include anacetyl group.

Examples of the alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8) of R^(1D), R^(2D), or R^(4D) include amethoxycarbonyl group or an ethoxycarbonyl group.

Examples of the C₁₋₈ alkylthio group of R^(1D), R^(2D), or R^(4D)include a methylthio group.

Examples of the C₁₋₈ alkylsulfinyl group of R^(1D), R^(2D), or R^(4D)include a methylsulfinyl group.

Examples of the C₁₋₈ alkylsulfonyl group of R^(1D), R^(2D), or R^(4D)include a methylsulfonyl group.

Examples of the hydroxyl-substituted C₁₋₈ alkyl group of R^(4D) includea hydroxymethyl group.

Examples of the optionally substituted benzenesulfonylamino group ofR^(4D) include a benzenesulfonylamino group and preferably ano-nitrobenzenesulfonylamino group optionally having a substituentselected from a C₁₋₈ alkyl group (e.g., a methyl group, an ethyl group),a C₁₋₈ alkoxy group (e.g., a methoxy group, an ethoxy group), a halogenatom (e.g., a fluorine atom, a chlorine atom), or a nitro group.

Examples of a preferable substituent of the optionally substitutedphenyl group of R^(4D) include a C₁₋₈ alkyl group such as a methyl orethyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atomssuch as a trifluoromethyl group, a halogen atom such as a fluorine atom,or a cyano group.

Examples of a preferable heterocyclic ring group in the optionallysubstituted heterocyclic ring group of R^(4D) include a tetrazolyl,triazolyl, pyridyl, imidazolyl, oxazolyl or thiazolyl group.

Examples of a preferable substituent of the optionally substitutedheterocyclic ring of R^(4D) include a C₁₋₈ alkyl group such as a methylor ethyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atomssuch as a trifluoromethyl group, a halogen atom such as a fluorine atom,a cyano group, or oxo.

Examples of

include a naphthalene ring, a tetrahydronaphthalene ring, or an indanering.

In general formula (DI), R^(1D), R^(2D), or R^(4D) substituents, whichare the same or different, may be present, in a ring having the R^(1D),R^(2D), or R^(4D) substituents.

Regarding the above listed examples, for R^(1D), R^(2D), R^(3D), orR^(4D) in general formula (DI), comprising a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group, a C₁₋₈ alkoxy group substituted with1 to 3 halogen atoms, a halogen atom, an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 3), a hydroxyl-substituted C₁₋₈alkyl group, a halogen atom, a C₁₋₈ alkylamino group, a C₁₋₅ alkylaminosubstituted with 1 to 5 halogen atoms, a C₂₋₈ dialkylamino group, a C₂₋₈acylamino group, a C₂₋₈ acylamino group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkylsulfonylamino group, an optionally substitutedbenzenesulfonylamino group, a C₂₋₈ acyl group, an alkoxycarbonyl group(the number of carbon atoms in an alkoxy moiety is from 1 to 8), a C₁₋₈alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group,an optionally substituted phenyl group, or an optionally substitutedheterocyclic ring group, the same applies to R^(11D), R^(12D), R^(13D),or R^(14D) in general formula (DII).

Regarding the optionally substituted heterocyclic ring group of R^(14D)in general formula (DII), examples of the substituent include a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a C₁₋₈ alkylamino group, and a C₂₋₈ dialkylaminogroup, examples of which are included in those listed for R^(1D) toR^(4D) in general formula (DI).

Examples of

include a naphthalene ring, a tetrahydronaphthalene ring, or an indanering.

In general formula (DII), R^(11D), R^(12D), or R^(14D) substituents,which are the same or different, may be present, in a benzene ringhaving the R^(11D), R^(12D), or R^(14D) substituents.

The following compounds are preferable as compounds represented bygeneral formula (DI).

(D-1-1) A compound described in (D-1), wherein R^(1D) and R^(2D) are thesame or different and are a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, or an amino group.

(D-1-2) A compound described in (D-1) or (D-1-1), wherein R^(3D) is ahydrogen atom or a C₁₋₈ alkyl group.

(D-1-3) A compound described in (D-1) or (D-1-1) or (D-1-2), whereinR^(4D) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C₁₋₈alkyl group, a halogen atom, a hydroxyl group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₁₋₈alkylsulfonylamino group, an optionally substituted benzenesulfonylaminogroup, an optionally substituted phenyl group, or an optionallysubstituted heterocyclic ring group.

(D-1-4) A compound described in (D-1) or any of (D-1-1) to (D-1-3),wherein R^(4D) is a 5- or 6-membered heterocyclic ring comprising 1 to 4atoms of nitrogen as a ring constituent element.

(D-1-5) A compound described in (D-1) or any of (D-1-1) to (D-1-4),wherein R^(4D) is a tetrazolyl, triazolyl, pyridyl, imidazolyl,oxazolyl, or thiazolyl group optionally having a substituent selectedfrom a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group.

(D-1-6) A compound described in (D-1) or any of (D-1-1) to (D-1-7),wherein R^(4D) is tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, or imidazole optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, a cyano group, an oxo group, or athioxo group.

(D-1-7) A compound described in (D-1) or any of (D-1-1) to (D-1-6),wherein R^(4D) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(D-1-8) A compound described in (D-1) or any of (D-1-1) to (D-1-7),wherein R^(4D) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(D-1-9) A compound described in (D-1) or any of (D-1-1) to (D-1-8),wherein R^(4D) is tetrazole.

(D-1-10) A compound described in (D-1) or any of (D-1-1) to (D-1-9),wherein R^(4D) is a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a hydroxyl group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₂₋₈ dialkylamino group, or a benzenesulfonylaminogroup optionally having a substituent selected from a C₁₋₈ alkyl group,a C₁₋₈ alkoxy group, a halogen atom, or a nitro group.

(D-1-11)

A compound described in (D-1) or any of (D-1-1) to (D-1-10), wherein

is a naphthalene ring, a tetrahydronaphthalene ring, or an indane ring.

(D-1-12)

A compound described in (D-1) or any of (D-1-1) to (D-1-11), wherein

is a benzene ring or an indole ring.

The following compounds are preferable as compounds represented bygeneral formula (DII).

(D-2-1) A compound described in (D-2), wherein R^(11D) and R^(12D) arethe same or different and are a hydrogen atom, a C₁₋₈ alkyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, or anamino group.

(D-2-2) A compound described in (D-2) or (D-2-1), wherein R^(13D) is ahydrogen atom.

(D-2-3) A compound described in (D-2) or (D-2-1) or (D-2-2), whereinR^(14D) is a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a hydroxyl-substituted C₁₋₈ alkyl group, a hydroxyl group, acyano group, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈dialkylamino group, a C₁₋₈ alkylsulfonylamino group, an optionallysubstituted benzenesulfonylamino group, an optionally substituted phenylgroup, or an optionally substituted heterocyclic ring group.

(D-2-4) A compound described in (D-2) or any of (D-2-1) to (D-2-3),wherein R^(14D) is a 5- or 6-membered heterocyclic ring comprising 1 to4 atoms of nitrogen as a ring constituent element.

(D-2-5) A compound described in (D-2) or any of (D-2-1) to (D-2-4),wherein R^(14D) is a tetrazolyl, triazolyl, pyridyl, imidazolyl,oxazolyl, or thiazolyl group optionally having a substituent selectedfrom a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group.

(D-2-6) A compound described in (D-2) or any of (D-2-1) to (D-2-5),wherein R^(14D) is tetrazole, 1,2,4-triazole, 1,2,3-triazole,1,2,4-oxadiazole, pyrazole, or imidazole optionally having a substituentselected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, a cyano group, an oxo group, or athioxo group.

(D-2-7) A compound described in (D-2) or any of (D-2-1) to (D-2-6),wherein R^(14D) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(D-2-8) A compound described in (D-2) or any of (D-2-1) to (D-2-7),wherein R^(14D) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(D-2-9) A compound described in (D-2) or any of (D-2-1) to (D-2-8),wherein R^(14D) is tetrazole.

(D-2-10) A compound described in (D-2) or any of (D-2-1) to (D-2-9),wherein R^(14D) is a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a hydroxyl group, a cyano group, an amino group, a C₁₋₈alkylamino group, a C₂₋₈ dialkylamino group, or a benzenesulfonylaminogroup optionally having a substituent selected from a C₁₋₈ alkyl group,a C₁₋₈ alkoxy group, a halogen atom, or a nitro group.

(D-2-11)

A compound described in (D-2) or any of (D-2-1) to (D-2-10), wherein

is a naphthalene ring.

The following shows representative compounds included in general formula(DI).

<Representative Compound D-100>

wherein R^(1D), R^(3D), and R^(4D) are as described in Table 51.

TABLE 51 R^(1D) R^(3D) R^(4D) H H 3-OH 8-Me H 3-OMe 8-Cl H 4-OH 9-Me H3,4-OH 9-Cl H 3-CN H H 4-CN H H 3-CO₂H H H 3-NH₂ H H 3-NHMe H Me 3-NHMeH Et 3-NHEt H H 3-NHCH₂CF₃ H H 3-NHSO₂Ph H H 3-NHSO₂(2-NO₂)Ph H H1H-Tetrazol-5-yl H H 1H-Tetrazol-1-yl H H (2-Methyl-2H-tetrazol)-5-yl HH 1,3-Oxazol-2-yl H H 1-H-Imidazol-2-yl H H (1,2,4-Triazol)-3-yl

<Representative Compound D-200>

wherein R^(1D), R^(3D), and T^(D) are as described in Table 52.

TABLE 52 R^(1D) R^(3D) T^(D) H H 1H-Indol-6-yl 8-Me H 1H-Indol-4-yl 8-ClH 1H-Indazol-6-yl 9-Me H 1H-Indazol-4-yl 9-Cl H 1H-Indolin-6-yl H Me1H-Benzimidazol-6-yl H Et 1H-Benzotriazol-6-yl H H3-Methylbenzisoxazol-6-yl H H Pyridin-3-yl H H 1H-Pyrazol-4-yl H HPyridin-2-yl H H 4-Methylpyridin-2-yl H H 2-Bromopyridin-5-yl

<Representative Compound D-300>

wherein A^(D)-B^(D)-D^(D)-E^(D), R^(3D), and R^(4D) are as described inTable 53.

TABLE 53 A^(D)-B^(D)-D^(D)-E^(D) R^(3D) R^(4D) CH₂CH₂CH₂CH₂ H 3-OHCH₂CH₂CH₂ H 3-OMe CH₂CH₂(CH₂)₂CH₂ H 4-OH CH₂CH₂(CH₂)₃CH₂ H 3,4-OHCH₂CH₂CH₂CH₂ H 3-CN CH₂CH₂NHCH₂ H 4-CN CH₂CH₂CH₂CH₂ H 3-CO₂H CH₂CH₂NHCH₂H 3-NH₂ CH₂CH₂CH₂CH₂ H 3-NHMe CH₂CH₂CH₂CH₂ Me 3-NHMe CH₂CH₂CH₂CH₂ Et3-NHEt CH₂CH₂CH₂CH₂ H 3-NHCH₂CF₃ CH₂CH₂CH₂CH₂ H 3-NHSO₂Ph CH₂CH₂CH₂CH₂ H3-NHSO₂(2-NO₂)Ph CH₂CH₂CH₂CH₂ H 1H-Tetrazol-5-yl CH₂NHCH₂CH₂ H1H-Tetrazol-1-yl CH₂CH(Me)CH₂CH₂ H (2-Methyl-2H-tetrazol)-5-ylCH₂CH(Me)CH₂CH₂ H 1,3-Oxazol-2-yl CH₂CH₂CH(Me)CH₂ H 1-H-Imidazol-2-ylCH₂CH₂CH(Me)CH₂ H (1,2,4-Triazol)-3-yl

<Representative Compound D-400>

wherein A^(D)-B^(D)-D^(D)-E^(D), R^(3D), and T^(D) are as described inTable 54.

TABLE 54 A^(D)-B^(D)-D^(D)-E^(D) R^(3D) T^(D) CH₂CH₂CH₂CH₂ H1H-Indol-6-yl CH₂CH₂CH₂ H 1H-Indol-4-yl CH₂CH₂(CH₂)₂CH₂ H1H-Indazol-6-yl CH₂CH₂(CH₂)₃CH₂ H 1H-Indazol-4-yl CH₂CH₂CH₂CH₂ Me1H-Indolin-6-yl CH₂NHCH₂CH₂ Et 1H-Benzimidazol-6-yl CH₂CH₂CH₂CH₂ H1H-Benzotriazol-6-yl CH₂CH₂CH₂CH₂ H 3-Methylbenzisoxazol-6-ylCH₂CH₂CH₂CH₂ H Pyridin-3-yl CH₂N(Me)CH₂CH₂ H 1H-Pyrazol-4-ylCH₂CH(Me)CH₂CH₂ H Pyridin-2-yl CH₂CH₂CH(Me)CH₂ H 4-Methylpyridin-2-ylCH₂CH₂CH(Me)CH₂ H 2-Bromopyridin-5-yl

(E-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (EI):

wherein R^(1E) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,or a phenyl-substituted C₁₋₃ alkyl group,

R^(2E) and R^(3E) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈dialkylamino group, a C₂₋₈ acylamino group, a C₂₋₈ acylamino groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkylsulfonylamino group,a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (the numberof carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoyl group,a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonylgroup, or a sulfamoyl group,

R^(4E) and R^(5E) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, or a phenyl-substituted C₁₋₃ alkyl group,

represents naphthalene or tetrahydronaphthalene,

W^(2E) represents an optionally substituted heterocyclic ring,

when X^(E) is N, Y^(E) is C═O and a double line composed of a solid lineand a dashed line denotes a single bond and

when X^(E) is C, Y^(E) is N and a double line composed of a solid lineand a dashed line denotes a double bond, and

P^(E) is 0 or 1.

Examples of the C₁₋₈ alkyl group of R^(1E), R^(2E), R^(3E), R^(4E), orR^(5E) in general formula (EI) include a methyl, ethyl, propyl,isopropyl, butyl, i-butyl, t-butyl, pentyl, or hexyl group.

Examples of the C₂₋₈ alkenyl group of R^(1E) include an allyl group.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsin R^(1E), R^(2E), R^(3E), R^(4E), or R^(5E) include a methyl, ethyl,propyl, isopropyl, butyl, or t-butyl group substituted with 1 to 3halogen atoms such as fluorine, chlorine, or bromine atoms, andpreferably a trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl,or 2-fluoroethyl group.

Examples of the phenyl-substituted C₁₋₃ alkyl group of R^(1E), R^(4E),or R^(5E) include a benzyl group.

Examples of the C₁₋₈ alkoxy group of R^(2E) or R^(3E) include a methoxy,ethoxy, propoxy, isopropoxy, butoxy, i-butoxy, t-butoxy, pentyloxy, orhexyloxy group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsin R^(2E) or R^(3E) include a methyl, ethyl, propyl, isopropyl, butyl,or t-butyl group substituted with 1 to 3 halogen atoms such as fluorine,chlorine, or bromine atoms, and preferably a trifluoromethoxy,2-chloroethoxy, 2-bromoethoxy, or 2-fluoroethoxy group.

Examples of the halogen atom of R^(2E) or R^(3E) include a fluorine,chlorine, or bromine atom.

Examples of the C₁₋₈ alkylamino group of R^(2E) or R^(3E) include amethylamino or ethylamino group.

Examples of the C₁₋₈ dialkylamino group of R^(2E) or R^(3E) include adimethylamino or diethylamino group.

Examples of the C₂₋₈ acylamino group of R^(2E) or R^(3E) include anacetylamino group.

Examples of the C₂₋₈ acylamino group substituted with 1 to 3 halogenatoms in R^(2E) or R^(3E) include a trifluoromethylcarbonylamino group.

Examples of the C₁₋₈ alkylsulfonylamino group of R^(2E) or R^(3E)include a methylsulfonylamino group.

Examples of the C₂₋₈ acyl group of R^(2E) or R^(3E) include an acetylgroup.

Examples of the alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8) of R^(2E) or R^(3E) include amethoxycarbonyl group or an ethoxycarbonyl group.

Examples of the C₁₋₈ alkylthio group of R^(2E) or R^(3E) include amethylthio group.

Examples of the C₁₋₈ alkylsulfinyl group of R^(2E) or R^(3E) include amethylsulfinyl group.

Examples of the C₁₋₈ alkylsulfonyl group of R^(2E) or R^(3E) include amethylsulfonyl group.

Examples of

include naphthalene or tetrahydronaphthalene.

The optionally substituted heterocyclic ring of W^(2E) represents a 5-or 6-membered heterocyclic ring comprising 1 to 4 atoms of nitrogen as aring constituent element.

Examples of the optionally substituted heterocyclic ring of W^(2E)include tetrazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,4-oxadiazole,pyrazole, imidazole, oxazole, isoxazole, pyrrole, thiazole, pyridine, orpyrrolidine.

Examples of an optional substituent of the optionally substitutedheterocyclic ring of W^(2E) include a C₁₋₈ alkyl group such as a methylor ethyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atomssuch as a trifluoromethyl group, a halogen atom such as a fluorine atom,a cyano group, an oxo group, or a thioxo group.

In general formula (EI), 1 to 3 R^(2E) or R^(3E) substituents, which arethe same or different, may be present, in a ring having the R^(2E) orR^(3E) substituents.

The following compounds are preferable as compounds represented bygeneral formula (EI).

(E-1-1) A compound described in (E-1), wherein W^(2E) is a 5- or6-membered heterocyclic ring comprising 1 to 4 atoms of nitrogen as aring constituent element.

(E-1-2) A compound described in (E-1) or (E-1-1), wherein W^(2E) istetrazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,4-oxadiazole, pyrazole,or imidazole optionally having a substituent selected from a C₁₋₈ alkylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, ahalogen atom, a cyano group, an oxo group, or a thioxo group.

(E-1-3) A compound described in (E-1) or any of (E-1-1) to (E-1-2),wherein W^(2E) is tetrazole, 1,2,4-triazole, or 1,2,3-triazoleoptionally having a substituent selected from a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or acyano group.

(E-1-4) A compound described in (E-1) or any of (E-1-1) to (E-1-3),wherein W^(2E) is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole.

(E-1-5) A compound described in (E-1) or any of (E-1-1) to (E-1-4),wherein W^(2E) is tetrazole.

(E-1-6)

A compound described in (E-1) or any of (E-1-1) to (E-1-5), wherein

is naphthalene or tetrahydronaphthalene.

(E-1-7)

A compound described in (E-1) or any of (E-1-1) to (E-1-6), wherein

is naphthalene.

(E-1-8) A compound described in (E-1) or any of (E-1-1) to (E-1-7),wherein R^(1E) is a hydrogen atom or a C₁₋₈ alkyl group.

(E-1-9) A compound described in (E-1) or any of (E-1-1) to (E-1-8),wherein R^(1E) is a hydrogen atom.

(E-1-10) A compound described in (E-1) or any of (E-1-1) to (E-1-9),wherein R^(4E) is a hydrogen atom and R^(SE) is a hydrogen atom or aC₁₋₈ alkyl group.

(E-1-11) A compound described in (E-1) or any of (E-1-1) to (E-1-10),wherein both R^(4F) and R^(5E) are a hydrogen atom.

(E-1-12) A compound described in (E-1) or any of (E-1-1) to (E-1-11),wherein R^(2E) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a carboxylgroup, a C₂₋₈ acyl group, or an alkoxycarbonyl group (the number ofcarbon atoms in an alkoxy moiety is from 1 to 8).

(E-1-13) A compound described in (E-1) or any of (E-1-1) to (E-1-12),wherein R^(2E) is a hydrogen atom.

(E-1-14) A compound described in (E-1) or any of (E-1-1) to (E-1-13),wherein R^(3E) is a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a carboxylgroup, a C₂₋₈ acyl group, or an alkoxycarbonyl group (the number ofcarbon atoms in an alkoxy moiety is from 1 to 8).

(E-1-15) A compound described in (E-1) or any of (E-1-1) to (E-1-14),wherein R^(3E) is a hydrogen atom.

(E-1-16) A compound described in (E-1) or any of (E-1-1) to (E-1-15),wherein X^(E) is N, Y^(E) is C═O, and the double line composed of asolid line and a dashed line denotes a single bond.

(E-1-17) A compound described in (E-1) or any of (E-1-1) to (E-1-15),wherein X^(E) is C, Y^(E) is N, and the double line composed of a solidline and a dashed line denotes a double bond.

(E-1-18) A compound described in (E-1) or any of (E-1-1) to (E-1-17),wherein P^(E) is 0 r 1.

(E-1-19) A compound described in (E-1) or any of (E-1-1) to (E-1-18),wherein P^(E) is 1.

<Representative Compound E-100>

The following shows representative compounds included in general formula(EI).

R^(1E), R^(4E), R^(5E), and W^(2E), and W^(2E) substitution positionsare as described in Tables 55 to 57.

In Tables 55 to 57, each W^(2E) substitution position indicates asubstitution position on a benzene ring. Specifically, positions 2, 3,and 4 in the tables correspond to positions 2′, 3′, and 4′,respectively, in the formula of representative compound E-100.

TABLE 55 W^(2E) SUBSTITUTION R^(1E) POSITION W^(2E) R^(4E)/R^(5E) H 2-1H-Tetrazol-5-yl H/H H 3- 1H-Tetrazol-5-yl H/H H 3-(1-Methyl-1H-tetrazol)-5-yl H/H H 4- 1H-Tetrazol-5-yl H/H Me 3-1H-Tetrazol-5-yl H/H Me 3- 1H-Tetrazol-5-yl Me/H Bn 3- 1H-Tetrazol-5-ylH/H H 3- 1H-Tetrazol-1-yl H/H H 3- 1H-Tetrazol-1-yl Me/Me H 3-(1,2,3-Triazol)-5-yl H/H H 3- (1,2,4-Triazol)-3-yl H/H H 4-(1,2,4-Triazol)-3-yl H/H

TABLE 56 W^(2E) SUBSTITUTION R^(1E) POSITION W^(2E) R^(4E)/R^(5E) H 2-(1,2,4-Triazol)-1-yl H/H H 3- (1,2,4-Triazol)-1-yl H/H H 3-[5-(Trifluoromethyl)-1,2,4-triazol]-3-yl H/H H 3-[5-(Trifluoromethyl)-1,2,4-triazol]-3-yl Et/H H 3-[5-Fluoro-1,2,3-triazol]-4-yl H/H H 3- [5-Fluoro-1,2,3-triazol]-4-ylMe/Me H 3- [5-Cyano-1,2,3-triazol]-4-yl H/H H 4- 1H-Imidazol-1-yl H/H H4- 1H-Imidazol-1-yl Pr/H H 3- 1H-Imidazol-2-yl H/H H 3- 1H-Imidazol-4-ylH/H H 3- Imidazolin-2-yl H/H

TABLE 57 W^(2E) SUBSTITUTION R^(1E) POSITION W^(2E) R^(4E)/R^(5E) H 2-Pyrazol-3-yl H/H H 3- Pyrazol-4-yl H/H H 3- Pyrazol-5-yl Me/H H 3-(1,2,4-Oxadiazol)-3-yl H/H H 3- (1,3,4-Oxadiazol)-2-yl H/H H 3-(5-Oxo-1,2,4-oxadiazol)-3-yl H/H H 3- Pyrrol-1-yl H/H H 4-Pyrrolidin-2-yl H/H Me 4- Pyrrolidin-2-yl Me/H H 4- (1,3-Oxazol)-5-ylH/H H 3- (1,3-Oxazol)-5-yl H/H H 2- (1,3-Thiazol)-5-yl H/H

<Representative Compound E-200>

wherein R^(1E), R^(2E), R^(4E), R^(5E), and W^(2E), and W^(2E)substitution positions are as described in Tables 58 and 59.

In Tables 58 and 59, each W^(2E) substitution position indicates asubstitution position on a benzene ring. Specifically, positions 2, 3,and 4 in the tables correspond to positions 2′, 3′, and 4′,respectively, in the formula of representative compound E-200.

TABLE 58 W^(2E) substitution R^(1E) R^(2E) position W^(2E) R^(4E)/R^(5E)H 4-OH 3- 1H-Tetrazol-5-yl H/H H 4-OMe 3- 1H-Tetrazol-5-yl H/H Me 2-Cl3- 1H-Tetrazol-5-yl H/H H 2,6-Cl 3- 1H-Tetrazol-5-yl H/H H 4-F 3-1H-Tetrazol-5-yl H/H H 4-Br 3- 1H-Tetrazol-5-yl Et/H H 3-OMe 4-(1-Methyl-1H-tetrazol)-5-yl H/H H 4-Me 3- 1H-Tetrazol-5-yl H/H

TABLE 59 W^(2E) substitution R^(1E) R^(2E) position W^(2E) R^(4E)/R^(5E)H 4-Cl 3- (1,2,3-Triazol)-5-yl Me/H H 4-CF₃ 3- (1,2,3-Triazol)-5-yl H/HH 3-SMe 4- (1,2,4-Triazol)-1-yl H/H H 3-SO₂Me 4- 1H-Imidazol-1-yl H/H H3-NHSO₂Me 4- 1H-Imidazol-1-yl H/H H 4-OMe 3- 1H-Imidazol-4-yl H/H H 4-F2- Pyrazol-3-yl H/H

<Representative Compound E-300>

wherein R^(1E), R^(2E), R^(3E), R^(4E), R^(5E), and W^(2E), and W^(2E)substitution positions are as described in Tables 60 and 61.

In Tables 60 and 61, each W^(2E) substitution position indicates asubstitution position on a benzene ring. Specifically, positions 3 and 4in the tables correspond to positions 3′ and 4′, respectively, in theformula of representative compound E-300.

TABLE 60 W^(2E) substitution R^(4E)/ R^(1E) R^(2E) position W^(2E)R^(3E) R^(5E) H H 3- 1H-Tetrazol-5-yl 9-Br H/H H 4-OMe 3-1H-Tetrazol-5-yl 9-Cl H/H H 4-OH 3- 1H-Tetrazol-5-yl 10-OMe H/H H 2-Cl3- 1H-Tetrazol-5-yl 9-Br H/H H 2,6-Cl 3- 1H-Tetrazol-5-yl 9-Me H/H H H3- 1H-Tetrazol-5-yl 10-Cl Me/H H 3-OMe 4- (1-Methyl-1H-tetrazol)-5-yl9-CF₃ H/H

TABLE 61 W^(2E) substitution R^(1E) R^(2E) position W^(2E) R^(3E)R^(4E)/R^(5E) H 4-Me 3- 1H-Tetrazol-1-yl 9-CN Pr/H Me H 3-(1,2,3-Triazol)-5-yl 9-OH H/H Et H 3- (1,2,3-Triazol)-5-yl 10-F H/H H3-Br 4- (1,2,4-Triazol)-1-yl 9-SMe H/H Allyl H 4- 1H-Imidazol-1-yl 8-OMeH/H H H 3- 1H-Imidazol-1-yl 10-OMe Me/Me

<Representative Compound E-400>

wherein W^(2E) and W^(2E) substitution positions are as described inTable 62.

In Table 62, each W^(2E) substitution position indicates a substitutionposition on a benzene ring. Specifically, positions 3 and 4 in the tablecorrespond to positions 3′ and 4′, respectively, in the formula ofrepresentative compound E-400.

TABLE 62 W^(2E) substitution position W^(2E) 3- 1H-Tetrazol-5-yl 4-1H-Tetrazol-5-yl 3- 5-Thioxo-1,2,4-oxadiazol-3-yl

<Representative Compound E-500>

wherein A^(E)-B^(E)-D^(E)-E^(E), R^(4E)/R^(5E), W^(2E), and R^(2E) areas described in Tables 63 to 65; and the “Position” in the tablesindicates a W^(2E) substitution position.

TABLE 63 R^(4E)/ Posi- A^(E)-B^(E)-D^(E)-E^(E) R^(5E) tion W^(2E) R^(2E)CH₂CH₂CH₂CH₂ H/H 3 1H-Tetrazol-5-yl H C(CH₃)₂CH₂CH₂CH₂ H/H 31H-Tetrazol-5-yl H C(CH₃)₂CH₂CH₂CH₂ H/H 3 1H-Tetrazol-1-yl 4-FC(CH₃)₂CH₂CH₂C(CH₃)₂ H/H 3 2-Methyl-2H-tetrazol-5-yl 3-FCH₂CH₂C(CH₃)₂CH₂ H/H 3 1,2,3-Triazol-5-yl 2-F CH₂CH₂CH₂CH₂ H/H 31,2,4-Triazol-3-yl H C(CH₃)₂CH₂CH₂C(CH₃)₂ H/H 31-Methyl-1H-tetrazoll-5-yl H CH₂CH₂CH₂CH₂ Me/ 3 Pyrazol-3-yl 4- H OHCH₂CH₂CH₂CH₂ Me/ 3 Pyrazol-4-yl H Me

TABLE 64 R^(4E)/ Posi- A^(E)-B^(E)-D^(E)-E^(E) R^(5E) tion W^(2E) R^(2E)C(CH₃)₂CH₂CH₂CH₂ H/H 3 5-Oxo-1,2,4-oxadiazol- 4- 3-yl NH₂CH₂C(CH₃)₂CH₂CH₂ CF₃/ 3 1,2,4-Oxadiazol-3-yl H H CH₂CH₂C(CH₃)₂CH₂ H/H 31,3,4-Oxadiazol-2-yl 4-F CH₂CH₂CH₂CH₂ H/H 4 Pyrrol-1-yl 3-FC(CH₃)₂CH₂CH₂C(CH₃)₂ H/H 3 5-Chloro-1H-imidazol- 4- 2-yl OH

TABLE 65 Posi- A^(E)-B^(E)-D^(E)-E^(E) R^(4E)/R^(5E) tion W^(2E) R^(2E)CH₂CH₂CH₂CH₂ Me/H 4 5-Methyl-1H-imidazol-2-yl 4-NH₂ CH₂CH₂CH₂CH₂ Me/H 45-Amino-1H-imidazol-2-yl 3-F CH₂CH₂CH₂CH₂ Me/H 32-Ethyl-2H-tetrazol-5-yl H C(CH₃)₂CH₂CH₂CH₂ Pr/H 32-(2,2,2-Trifluoroethyl)-2H- 2,6-F tetrazol-5-yl CH₂C(CH₃)₂CH₂CH₂ H/H 31,3-Oxazol-2-yl H CH₂CH₂C(CH₃)₂CH₂ H/H 3 1,3-Thiazol-2-yl H CH₂CH₂CH₂CH₂H/H 4 3,5-Dimethylisoxazol-4-yl H

<Representative Compound E-600>

wherein R^(3E), R^(1E), W^(2E), and R^(2E) are as described in Tables 66to 68; and the “W^(2E) position” in the tables indicates a W^(2E)substitution position on a benzene ring.

TABLE 66 W^(2E) R^(3E) R^(1E) position W^(2E) R^(2E) H H 31H-Tetrazol-5-yl H H H 4 1H-Tetrazol-5-yl H 8-Me H 3 1H-Tetrazol-5-yl H8-Cl H 3 1H-Tetrazol-5-yl H H H 3 1H-Tetrazol-5-yl 4-F H H 31H-Tetrazol-5-yl 4-Me H H 3 1H-Tetrazol-5-yl 5-Br H H 3 1H-Tetrazol-5-yl6-Me H H 3 1H-Tetrazol-5-yl 6-Cl H H 3 (5-Thioxo-1,2,4-oxadiazol)-3-yl HH H 3 (5-Oxo-1,2,4-oxadiazol)-3-yl H H H 3(5-Cyano-1H-1,2,3-triazol)-4-yl H

TABLE 67 W^(2E) R^(3E) R^(1E) position W^(2E) R^(2E) H H 31H-Tetrazol-5-yl 6-OH H H 3 (2-Methyl-2H-tetrazol)-5-yl H H Me 3(2-Methyl-2H-tetrazol)-5-yl H H Et 3 (2-Ethyl-2H-tetrazol)-5-yl H H H 3(1-Methyl-1H-tetrazol)-5-yl H H H 34-Methyl-(5-thioxo-1,2,4-oxadiazol)-3-y1 H H H 31-Methyl-1H-imidazol-2-yl H H H 3 1-Methyl-1H-imidazol-4-yl H H H 31,3-Oxazol-2-yl H H H 3 1,3-Thiazol-2-yl H H H 3 Pyrrol-2-yl H H H 3Thiophen-2-yl H H H 3 1-H-Imidazol-2-yl H H H 3 1-H-Imidazol-4-yl H

TABLE 68 W^(2E) R^(3E) R^(1E) position W^(2E) R^(2E) H H 3 Pyrazol-4-ylH H H 3 5-(Chloro)-1H-imidazol-2-yl H H H 35-(Trifluoromethyl)-1H-imidazol-2-yl H H H 3 (1,2,3-Triazol)-4-yl H H H3 (1,2,4-Triazol)-3-yl H H H 3 3-Methyl-(1,2,4-oxadiazol)-5-yl H H H 33,5-Dimethylisoxazol-4-yl H H H 3 1-Tetrazol-1-yl H H H 3 Pyridin-3-yl HH H 3 Pyrimidin-5-yl H H H 3 2-Aminopyridin-5-yl H

<Representative Compound E-700>

wherein A^(E)-B^(E)-D^(E)-E^(E), R^(1E), W^(2E), and R^(2E) are asdescribed in Tables 69 to 71; and the “W^(2E) position” in the tablesindicates a W^(2E) substitution position on a benzene ring.

TABLE 69 W^(2E) A^(E)-B^(E)-D^(E)-E^(E) R^(1E) position W^(2E) R^(2E)CH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl H CH₂CH₂CH₂CH₂ H 4 1H-Tetrazol-5-yl HCH₂NHCH₂CH₂ H 3 1H-Tetrazol-5-yl H CH₂CH₂OCH₂ H 3 1H-Tetrazol-5-yl 4-FCH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 4-Me CH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl5-Br CH₂CH₂CH₂CH₂ H 3 1H-Tetrazol-5-yl 6-Me CH₂CH₂CH₂CH₂ H 31H-Tetrazol-5-yl 6-Cl CH₂CH₂CH₂CH₂ H 3 (5-Thioxo-1,2,4-oxadiazol)-3-yl HCH₂CH₂CH₂CH₂ H 4 (5-Oxo-1,2,4-oxadiazol)-3-yl H

TABLE 70 W^(2E) A^(E)-B^(E)-D^(E)-E^(E) R^(1E) position W^(2E) R^(2E)CH₂CH₂CH₂CH₂ H 3 (5-Cyano-1H-1,2,3-triazol)-4-yl H CH₂CH₂CH₂CH₂ H 31H-Tetrazol-5-yl 6- OH CH₂CH₂CH₂CH₂ H 3 (2-Methyl-2H-tetrazol)-5-yl HCH₂CH₂CH₂CH₂ Me 3 (2-Methyl-2H-tetrazol)-5-yl H CH₂CH₂CH₂CH₂ Et 3(2-Ethyl-2H-tetrazol)-5-yl H CH₂NHCH₂CH₂ H 3 (1-Methy1-1H-tetrazol)-5-ylH CH₂CH₂CH₂CH₂ H 3 4-Methyl-(5-thioxo-1,2,4- H oxadiazol)-3-ylCH₂CH₂CH₂CH₂ H 3 1-Methyl-1 H-imidazol-2-yl H CH₂CH₂CH₂CH₂ H 31-Methyl-1 H-imidazol-4-yl H CH₂CH₂CH₂CH₂ H 3 1,3-Oxazol-2-yl HCH₂CH₂CH₂CH₂ H 3 1,3-Thiazol-2-yl H CH₂CH₂CH₂CH₂ H 3 Pyrrol-2-yl HCH₂CH₂CH₂CH₂ H 3 Thiophen-2-yl H

TABLE 71 W^(2E) posi- A^(E)-B^(E)-D^(E)-E^(E) R^(1E) tion W^(2E) R^(2E)CH₂CH₂CH₂CH₂ H 3 1-H-Imidazol-2-yl H CH₂CH₂CH₂CH₂ H 3 1-H-Imidazol-4-ylH CH₂CH₂CH₂CH₂ H 4 Pyrazol-4-yl H CH₂CH₂CH₂CH₂ H 35-(Chloro)-1H-imidazol-2-yl H CH₂CH₂CH₂CH₂ H 3 5-(Trifluoromethyl)-1H- Himidazol-2-yl CH₂CH₂CH₂CH₂ H 3 (1,2,3-Triazol)-4-yl H CH₂CH₂CH₂CH₂ H 3(1,2,4-Triazol)-3-yl H CH₂CH₂CH₂CH₂ H 3 3-Methyl-(1,2,4-oxadiazol)- H5-yl CH₂CH₂CH₂CH₂ H 4 3,5-Dimethylisoxazol-4-yl H CH₂CH₂CH₂CH₂ H 31-Tetrazol-1-yl H CH₂CH₂CH(Me)CH₂ H 3 Pyrimidin-5-yl H

<Representative Compound E-800>

wherein R^(3E), R^(1E), and W^(2E) are as described in Table 72.

TABLE 72 R^(3E) R^(1E) W^(2E) H H 1H-Tetrazol-5-yl H H 1H-Tetrazol-1-ylH H (2-Methyl-2H-tetrazol)-5-yl H H 1,3-Oxazol-2-yl H H1-H-Imidazol-2-yl H H (1,2,4-Triazol)-3-yl

<Representative Compound E-900>

wherein A^(E)-B^(E)-D^(E)-E^(E), R^(1E), and W^(2E) are as described inTable 73.

TABLE 73 A^(E)-B^(E)-D^(E)-E^(E) R^(1E) W^(2E) CH₂CH₂CH₂CH₂ H1H-Tetrazol-5-yl CH₂CH(Me)CH₂CH₂ H (2-Methyl-2H-tetrazol)-5-ylCH₂CH(Me)CH₂CH₂ H 1,3-Oxazol-2-yl CH₂CH₂CH(Me)CH₂ H 1-H-Imidazol-2-ylCH₂CH₂CH(Me)CH₂ H (1,2,4-Triazol)-3-yl

(F-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (FI):

wherein R^(1F) and R^(2F) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), an optionally substituted phenyl group, an optionallysubstituted pyridyl group, or an aralkyl group (the number of carbonatoms in an aryl moiety is from 6 to 10 and the number of carbon atomsin an alkylene moiety is from 1 to 8), or

R^(1F) and R^(2F) are optionally fused with a benzene ring bondedthereto to form a condensed ring selected from a naphthalene ring, aquinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, anindane ring, a tetrahydroquinoline ring, or tetrahydroisoquinoline ringand a ring fused with R^(1F) and R^(2F) and comprising carbon atomsbonded to respective R^(1F) and R^(2F) is optionally substituted with 1to 4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₃_₈ cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),

R^(3F) and R^(4F) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, a nitro group, a cyano group, an amino group, a C₁₋₈ alkylaminogroup, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxylgroup, a C₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbonatoms in an alkoxy moiety is from 1 to 8), or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8),

R^(5F) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, ahydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (the numberof carbon atoms in an aryl moiety is from 6 to 10 and the number ofcarbon atoms in an alkylene moiety is from 1 to 8),

R^(6F) and R^(7F) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, or an amino group,

X^(F) represents C, CH, or N,

Y^(F) represents N, NH, or C(═O),

provided that when X^(F) is N, Y^(F) is neither N nor NH, and

when X^(F) is C or CH, Y^(F) is not C(═O),

a double line composed of a solid line and a dashed line denotes asingle bond or a double bond,

Z^(F) represents an oxygen atom or a sulfur atom,

A^(F) represents a bond or represents a benzene ring, a pyridine ring, athiophene ring, a pyrimidine ring, a naphthalene ring, a quinoline ring,or an indole ring optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, an aralkyl group (the number of carbon atoms inan aryl moiety is from 6 to 10 and the number of carbon atoms in analkylene moiety is from 1 to 8), a phenyl group, or a pyridyl group,

B^(F) represents N(R^(8F))C(═O), NHCONH, CON(R^(9F)), NHC(═S)NH,N(R^(10F)) SO₂, SO₂N(R^(11F)), or OSO₂,

R^(8F), R^(9F), R^(10F), and R^(11F) here represent a hydrogen atom, aC₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a hydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8),

D^(F) represents a bond or a C₁₋₆ alkylene chain optionally having, assubstituents, 1 to 4 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C₁₋₈alkyl group, or an aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 8) and further optionally having a double bond,

E^(F) represents O, S, NR^(12F), or a bond,

R^(12F) here represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a hydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (the numberof carbon atoms in an aryl moiety is from 6 to 10 and the number ofcarbon atoms in an alkylene moiety is from 1 to 8),

G^(F) represents piperazine, piperidine, morpholine, cyclohexane,benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene,imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine orpyrimidine optionally having, as substituents, 1 to 4 substituents,which are the same or different, selected from a C₁₋₈ alkyl group, aC₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acyl group, a methylenedioxy group, a carboxyl group, aC₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, a C₁₋₆ alkylsulfonylgroup, an aralkyl group (the number of carbon atoms in an aryl moiety isfrom 6 to 10 and the number of carbon atoms in an alkylene moiety isfrom 1 to 8), an optionally substituted phenyl, an optionallysubstituted pyridyl group, an optionally substituted imidazolyl group,an optionally substituted oxazolyl group, or an optionally substitutedthiazolyl group, and

m^(F) represents an integer of 0 to 5,

provided that a case is excluded where R^(1F) and R^(2F) are not fusedto form a ring and where X^(F) is C, Y^(F) is N, the double linecomposed of a solid line and a dashed line denotes a double bond, Z^(F)is an oxygen atom, A^(F) is a benzene ring, m^(F) is 0, B^(F) isC(═O)NH, E^(F) is a bond, and G^(F) is a phenyl group.

(F-2) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (FII):

wherein

represents a naphthalene ring, a quinoline ring, an isoquinoline ring, atetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring,or a tetrahydroisoquinoline ring,

the rings are optionally substituted with 1 to 4 substituents, which arethe same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, aC₂₋₈ acylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), or an aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 8),

R^(3Fa) and R^(4Fa) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, a nitro group, a cyano group, an amino group, a C₁₋₈ alkylaminogroup, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxylgroup, a C₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbonatoms in an alkoxy moiety is from 1 to 8), or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8),

R^(5Fa) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, ahydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (the numberof carbon atoms in an aryl moiety is from 6 to 10 and the number ofcarbon atoms in an alkylene moiety is from 1 to 8),

R^(6Fa) and R^(7Fa) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, or an amino group,

represents a benzene ring, a pyridine ring, a thiophene ring, apyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ringoptionally having, as substituents, 1 to 4 substituents, which are thesame or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),a phenyl group, or a pyridyl group,

B^(Fa) represents N(R^(8Fa))C(═O), NHCONH, CON(R^(9Fa)), NHC(═S)NH,N(R^(10Fa))SO₂, SO₂N(R^(11Fa)), or OSO₂,

R^(8Fa), R^(9Fa), R^(10Fa), and R^(11Fa) here represent a hydrogen atom,a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a hydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8),

E^(Fa) represents O, S, NR^(12Fa), or a bond,

R^(12Fa) here represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a hydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (the numberof carbon atoms in an aryl moiety is from 6 to 10 and the number ofcarbon atoms in an alkylene moiety is from 1 to 8),

G^(Fa) represents piperazine, piperidine, morpholine, cyclohexane,benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene,imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine orpyrimidine optionally having, as substituents, 1 to 4 substituents,which are the same or different, selected from a C₁₋₈ alkyl group, aC₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acyl group, a methylenedioxy group, a carboxyl group, aC₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, a C₁₋₆ alkylsulfonylgroup, an aralkyl group (the number of carbon atoms in an aryl moiety isfrom 6 to 10 and the number of carbon atoms in an alkylene moiety isfrom 1 to 8), an optionally substituted phenyl, an optionallysubstituted pyridyl group, an optionally substituted imidazolyl group,an optionally substituted oxazolyl group, or an optionally substitutedthiazolyl group, and

n^(F) represents an integer of 0 to 5.

Next, the present invention will be described in detail.

As used herein, examples of the C₁₋₈ alkyl group include a methyl,ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl, or hexylgroup.

Examples of the C₃₋₈ cycloalkyl group include a cyclopropyl group or acyclohexyl group.

Examples of the C₂₋₈ alkenyl group include an allyl group.

Examples of the C₁₋₈ alkoxy group include a methoxy, ethoxy, propoxy,isopropoxy, butoxy, i-butoxy, t-butoxy, pentyloxy, or hexyloxy group.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsinclude a methyl, ethyl, propyl, isopropyl, butyl, or t-butyl groupsubstituted with 1 to 3 halogen atoms such as fluorine, chlorine, orbromine atoms, and preferably a trifluoromethyl, chloromethyl,2-chloroethyl, 2-bromoethyl, or 2-fluoroethyl group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsinclude a methoxy, ethoxy, propoxy, isopropoxy, butoxy, or t-butoxygroup substituted with 1 to 3 halogen atoms such as fluorine, chlorine,or bromine atoms, and preferably a trifluoromethoxy, chloromethoxy,2-chloroethoxy, 2-bromoethoxy, or 2-fluoroethoxy group.

Examples of the halogen atom include a fluorine, chlorine, or bromineatom.

Examples of the C₁₋₈ alkylamino group include a methylamino orethylamino group.

Examples of the C₂₋₈ dialkylamino group include a dimethylamino ordiethylamino group.

Examples of the C₂₋₈ acylamino group include an acetylamino group.

Examples of the C₂₋₈ acyl group include an acetyl group.

Examples of the alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8) include a methoxycarbonyl group.

Examples of the aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 8) include a benzyl group.

Examples of the hydroxyl-substituted C₁₋₈ alkyl group include2-hydroxyethyl group.

Examples of the C₁₋₆ alkylsulfinyl group include a methanesulfinylgroup.

Examples of the C₁₋₆ alkylthio group include a methylthio group.

Examples of the C₁₋₆ alkylsulfonyl group include a methanesulfonylgroup.

Examples of an optional substituent of the optionally substituted phenylgroup, optionally substituted pyridyl group, optionally substitutedimidazolyl group, optionally substituted oxazolyl group, or optionallysubstituted thiazolyl group include a halogen atom, a C₁₋₈ alkyl group,a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, or a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms.

The following compounds are preferable as compounds represented bygeneral formula (FI).

(F-1-1)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1), wherein R^(1F) and R^(2F) are the same ordifferent and represent a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, an optionally substituted phenyl group, anoptionally substituted pyridyl group, or an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 8).

(F-1-2)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or (F-1-1), wherein R^(1F) and R^(2F) are fusedwith a benzene ring bonded thereto to form a naphthalene ring or atetrahydronaphthalene ring, and a cyclohexene ring or the benzene ringfused with R^(1F) and R^(2F) and comprising carbon atoms bonded torespective R^(1F) and R^(2F) is optionally substituted with 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxyl group, aC₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbon atoms inan alkoxy moiety is from 1 to 8), or an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 8).

(F-1-3)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or (F-1-1), wherein R^(1F) and R^(2F) are fusedwith a benzene ring bonded thereto to form a naphthalene ring, and thebenzene ring fused with R^(1F) and R^(2F) and having carbon atoms bondedto respective R^(1F) and R^(2F) is optionally substituted with 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,or an amino group.

(F-1-4)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or (F-1-1), wherein R^(1F) and R^(2F) are fusedwith a benzene ring bonded thereto to form a naphthalene ring or atetrahydronaphthalene ring.

(F-1-5)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-4), wherein R^(3F) andR^(4F) are the same or different and are a hydrogen atom, a C₁₋₈ alkylgroup, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, or an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 8).

(F-1-6)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-5), wherein R^(5F) is ahydrogen atom, a C₁₋₈ alkyl group, or an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 8).

(F-1-7)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-6), wherein R^(5F) is ahydrogen atom.

(F-1-8)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-7), wherein R^(6F) andR^(7F) are the same or different and are a hydrogen atom, a C₁₋₈ alkylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, or a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms.

(F-1-9)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-8), wherein both R^(6F)and R^(7F) are a hydrogen atom.

(F-1-10)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-9), wherein R^(3F),R^(4F), R^(5F), R^(6F), and R^(7F) are a hydrogen atom.

(F-1-11)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-10), wherein X^(F) is N,Y^(F) is C(═O), and the double line composed of a solid line and adashed line denotes a single bond.

(F-1-12)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-11), wherein X^(F) is C,Y^(F) is N, the double line composed of a solid line and a dashed lineis a double bond.

(F-1-13)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-12), wherein Z^(F) is anoxygen atom.

(F-1-14)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-13), wherein A^(F) is aphenyl group or a pyridyl group optionally having, as substituents, 1 to4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, an aralkyl group (the number of carbon atoms inan aryl moiety is from 6 to 10 and the number of carbon atoms in analkylene moiety is from 1 to 8), a phenyl group, or a pyridyl group.

(F-1-15)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-14), wherein A^(F)represents a phenyl group optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, or an amino group.

(F-1-16)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-15), wherein A^(F) is aphenyl group or a pyridyl group.

(F-1-17)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-16), wherein A^(F) is abond.

(F-1-18)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-17), wherein B^(F) isNHC(═O), NHCONH, CONH, NHC(═S)NH, NHSO₂, SO₂NH, or OSO₂.

(F-1-19)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-18), wherein B^(F) isNHC(═O), NHCONH, or NHSO₂.

(F-1-20)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-19), wherein B^(F) isNHC(═O) or NHSO₂.

(F-1-21)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-20), wherein B^(F) isNHC(═O).

(F-1-22)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-21), wherein D^(F) is aC₁₋₆ alkylene chain optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group or a C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsand further optionally having a double bond.

(F-1-23)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-22), wherein D^(F) is abond.

(F-1-24)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-23), wherein D^(F) has,as substituents, 1 to 4 substituents, which are the same or different,selected from a C₁₋₈ alkyl group or a C₂₋₈ alkenyl group.

(F-1-25)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-24), wherein D^(F) has,as substituents, 1 to 4 substituents, which are the same or different,selected from a C₁₋₃ alkyl group or a C₂₋₃ alkenyl group.

(F-1-26)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-25), wherein E^(F) is abond.

(F-1-27)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-26), wherein G^(F)represents piperazine, piperidine, morpholine, cyclohexane, benzene,naphthalene, quinoline, quinoxaline, benzimidazole, thiophene,imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine, orpyrimidine optionally having, as substituents, 1 to 4 substituents,which are the same or different, selected from a C₁₋₈ alkyl group, aC₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acyl group, a methylenedioxy group, a carboxyl group, aC₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, or a C₁₋₆alkylsulfonyl group.

(F-1-28)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-27), wherein G^(F) isbenzene optionally having, as substituents, 1 to 4 substituents, whichare the same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acyl group, a methylenedioxy group, a carboxyl group, aC₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, or a C₁₋₆alkylsulfonyl group.

(F-1-29)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-28), wherein G^(F) isbenzene or pyridine optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, a nitro group, an amino group, a C₂₋₈ dialkylamino group, acarboxyl group, a C₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, or aC₁₋₆ alkylsulfonyl group.

(F-1-30)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-29), wherein G^(F) isbenzene optionally having, as substituents, 1 to 4 substituents, whichare the same or different, selected from a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

(F-1-31)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-30), wherein m^(F) is 0.

(F-1-32)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-31), wherein A^(F) is abenzene ring, m^(F) is 0, B^(F) is NHC(═O) or NHSO₂, D^(F) is a C₁₋₃alkyl group or a bond, E^(F) is a bond, and G^(F) represents benzeneoptionally having, as substituents, 1 to 4 substituents, which are thesame or different, selected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxylgroup.

(F-1-33)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any of (F-1-1) to (F-1-32), wherein A^(F) is abenzene ring, m^(F) is 0, B^(F) is NHC(═O), D^(F) is a bond, E^(F) is abond, and G^(F) represents benzene optionally having, as substituents, 1to 4 substituents, which are the same or different, selected from a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or ahydroxyl group.

(F-1-34)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-1) or any one of (F-1-1) to (F-1-33), wherein R^(1F)and R^(2F) are fused with a benzene ring bonded thereto to form anaphthalene ring, R^(3F), R^(4F), R^(5F), R^(6F), and R^(7F) represent ahydrogen atom, X^(F) is N, Y^(F) is C(═O), the double line composed of asolid line and a dashed line denotes a single bond, Z^(F) represents anoxygen atom, A^(F) represents a benzene ring, m^(F) represents 0, B^(F)represents NHC(═O) or NHSO₂, D^(F) represents a C₁₋₃ alkyl group or abond, E^(F) represents a bond, and G^(F) represents benzene optionallyhaving, as substituents, 1 to 4 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxylgroup.

(F-1-35)

In the above general formula (FI), a compound, a tautomer, stereoisomer,or pharmaceutically acceptable salt of the compound, or a hydrate orsolvate thereof, the compound represented by (F-1) or any one of (F-1-1)to (F-1-34), wherein R^(1F) and R^(2F) are fused with a benzene ringbonded thereto to form a naphthalene ring, R^(3F), R^(4F), R^(5F),R^(6F), and R^(7F) represent a hydrogen atom, X^(F) is N, Y^(F) isC(═O), the double line composed of a solid line and a dashed linedenotes a single bond, Z^(F) represents an oxygen atom, A^(F) representsa benzene ring, m^(F) represents 0, B^(F) represents NHC(═O), D^(F)represents a bond, E^(F) represents a bond, and G^(F) represents benzeneoptionally having, as substituents, 1 to 4 substituents, which are thesame or different, selected from a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, or a hydroxyl group.

The following compounds are preferable as compounds represented bygeneral formula (FII).

(F-2-1)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2), wherein

is a naphthalene ring or a tetrahydronaphthalene ring optionallysubstituted with, as substituents, 1 to 4 substituents, which are thesame or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, aC₂₋₈ acylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), or an aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 8).

(F-2-2)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or (F-2-1), wherein

is a naphthalene ring optionally substituted with, as substituents, 1 to4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,or an amino group.

(F-2-3)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-2), wherein R^(3Fa) andR^(4Fa) are the same or different and are a hydrogen atom, a C₁₋₈ alkylgroup, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, or an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 8).

(F-2-4)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-3), wherein R^(5Fa) is ahydrogen atom, a C₁₋₈ alkyl group, or an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 8).

(F-2-5)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-4), wherein R^(5Fa) is ahydrogen atom.

(F-2-6)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-5), wherein R^(6Fa) andR^(7Fa) are the same or different and are a hydrogen atom, a C₁₋₈ alkylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, or a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms.

(F-2-7)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-6), wherein both R^(6Fa)and R^(7Fa) are a hydrogen atom.

(F-2-8)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-7), wherein

is a phenyl group or a pyridyl group optionally having, as substituents,1 to 4 substituents, which are the same or different, selected from aC₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, an aralkyl group (the number of carbon atoms inan aryl moiety is from 6 to 10 and the number of carbon atoms in analkylene moiety is from 1 to 8), a phenyl group, or a pyridyl group.

(F-2-9)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-8), wherein

is a phenyl group optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, or an amino group.

(F-2-10)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-9), wherein

is a bond.

(F-2-11)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-10), wherein B^(Fa) isNHC(═O), NHCONH, CONH, NHC(═S)NH, NHSO₂, SO₂NH, or OSO₂.

(F-2-12)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-11), wherein B^(Fa) isNHC(═O), NHCONH, or NHSO₂.

(F-2-13)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-12), wherein E^(Fa) is abond.

(F-2-14)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-13), wherein G^(Fa) ispiperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene,quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole,oxazole, indole, benzofuran, pyrrole, pyridine, or pyrimidine optionallyhaving, as substituents, 1 to 4 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylgroup, a methylenedioxy group, a carboxyl group, a C₁₋₆ alkylsulfinylgroup, a C₁₋₆ alkylthio group, or a C₁₋₆ alkylsulfonyl group.

(F-2-15)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-14), wherein G^(Fa) isbenzene optionally having, as substituents, 1 to 4 substituents, whichare the same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acyl group, a methylenedioxy group, a carboxyl group, aC₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, or a C₁₋₆alkylsulfonyl group.

(F-2-16)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (F-2) or any of (F-2-1) to (F-2-15), wherein n^(F) is 0.

In the above general formula (FI), it is preferable that R^(F1) andR^(F2) are fused with a benzene ring bonded thereto to form a condensedring selected from a naphthalene ring or a tetrahydronaphthalene ring.It is particularly preferable to form a naphthalene ring.

In the above general formula (FI), it is preferable that R^(F3), R^(F4),R^(F5), R^(F6), and R^(F7) represent a hydrogen atom.

In the above general formula (FI), it is preferable that X^(F) is N,Y^(F) is C(═O), and the double line composed of a solid line and adashed line is a single bond.

In the above general formula (FI), it is preferable that Z^(F) is anoxygen atom.

In the above general formula (FI), it is preferable that A^(F)represents a benzene ring or a pyridine ring. It is particularlypreferable that A^(F) represents a benzene ring.

In the above general formula (FI), it is preferable that m^(F)represents from 0 to 4. It is particularly preferable that m^(F)represents 0.

In the above general formula (FI), it is preferable that B^(F)represents N(R^(8F))C(═O) or N(R^(10F))SO₂. At this time, it is morepreferable that R^(8F) and R^(11F) represent a hydrogen atom. In theabove general formula (FI), it is particularly preferable that B^(F)represents NHC(═O).

In the above general formula (FI), it is preferable that D^(F)represents a bond or has, as substituents, 1 to 4 substituents, whichare the same or different, selected from a C₁₋₈ alkyl group or a C₂₋₈alkenyl group. It is particularly preferable that D^(F) represents abond or has, as substituents, 1 to 4 substituents, which are the same ordifferent, selected from a C₁₋₃ alkyl group or a C₂₋₃ alkenyl group.

In the above general formula (FI), it is preferable that E^(F)represents O or a bond. It is particularly preferable that E^(F)represents a bond.

In the above general formula (FI), it is preferable that G^(F)represents benzene or pyridine optionally having, as substituents, 1 to4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, a nitro group, an amino group, a C₂₋₈ dialkylamino group, acarboxyl group, a C₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, or aC₁₋₆ alkylsulfonyl group. It is particularly preferable that G^(F)represents benzene optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or ahydroxyl group.

In the above general formula (FI), it is preferable that A^(F)represents a benzene ring, m^(F) represents 0, B^(F) represents NHC(═O)or NHSO₂, D^(F) represents a C₁₋₃ alkyl group or a bond, E^(F)represents a bond, and G^(F) represents benzene optionally having, assubstituents, 1 to 4 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a halogen atom, or a hydroxyl group.

In the above general formula (FI), it is preferable that A^(F)represents a benzene ring, m^(F) represents 0, B^(F) represents NHC(═O),D^(F) represents a bond, E^(F) represents a bond, and G^(F) representsbenzene optionally having, as substituents, 1 to 4 substituents, whichare the same or different, selected from a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

In the above general formula (FI), it is more preferable that R^(F1) andR^(F2) are fused with a benzene ring bonded thereto to form anaphthalene ring, R^(F3), R^(F4), R^(F5), R^(F6), and R^(F7) represent ahydrogen atom, X^(F) is N, Y^(F) is C(═O), the double line composed of asolid line and a dashed line denotes a single bond, Z^(F) represents anoxygen atom, A^(F) represents a benzene ring, m^(F) represents 0, B^(F)represents NHC(═O) or NHSO₂, D^(F) represents a C₁₋₃ alkyl group or abond, E^(F) represents a bond, and GF represents benzene optionallyhaving, as substituents, 1 to 4 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxylgroup.

In the above general formula (FI), it is particularly preferable thatR^(F1) and R^(F2) are fused with a benzene ring bonded thereto to form anaphthalene ring, R^(F3), R^(F4), R^(F5), R^(F6), and R^(F7) represent ahydrogen atom, X^(F) is N, Y^(F) is C(═O), the double line composed of asolid line and a dashed line denotes a single bond, Z^(F) represents anoxygen atom, A^(F) represents a benzene ring, m^(F) represents 0, B^(F)represents NHC(═O), D^(F) represents a bond, E^(F) represents a bond,and G^(F) represents benzene optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, or ahydroxyl group.

The following shows representative compounds included in general formula(FI) and/or (FII).

<Representative Compound F-100>

wherein B^(Fa) (substitution position), n^(F), E^(Fa), and G^(Fa) are asdescribed in Tables 74 to 83.

TABLE 74 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 0Bond Phenyl NHCO(4) 0 Bond (2-CF₃)Phenyl NHCO(4) 0 Bond (3-Br)PhenylNHCO(4) 0 Bond (4-CF₃)Phenyl NHCO(4) 0 Bond (2-Me)Phenyl NHCO(4) 0 Bond(2,6-Me)Phenyl NHCO(4) 0 Bond (2,6-Cl)Phenyl NHCO(4) 0 Bond (3-Cl)PhenylNHCO(4) 1 Bond Phenyl NHC(═S)NH(4) 0 Bond Phenyl NHCO(4) 0 Bond(2,3-OMe)Phenyl NHCO(4) 0 Bond (2-OMe)Phenyl NHCO(4) 1 Bond (2-Cl)PhenylNHCO(4) 0 Bond (2,3-Me)Phenyl NHCO(4) 0 Bond (2,5-Me)Phenyl NHCO(4) 0Bond (2-Cl,5-Br)Phenyl

TABLE 75 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 0Bond (2,4-Cl)Phenyl NHCO(4) 0 Bond (2-OH)Phenyl NHCO(4) 0 Bond(2,3-OH)Phenyl NHC(═O)NH(4) 0 Bond Phenyl NHCO(4) 1 Bond (2,6-Cl)PhenylNHCO(4) 1 Bond (2-OMe)Phenyl NHCO(4) 1 Bond (2-OH)Phenyl NHC(═S)NH(4) 0Bond (2-Cl)Phenyl NHCO(4) 0 Bond (3-CF₃)Phenyl NHCO(4) 1 Bond(2-CF₃)Phenyl NHC(═O)NH(4) 0 Bond (2-Cl)Phenyl NHCO(4) 0 Bond(2-Cl,3-OMe)Phenyl NHCO(4) 2 Bond Phenyl NHCO(4) 0 Bond 3-indolylNHCO(4) 0 Bond (2-Cl,3-OH)Phenyl NHCO(4) 1 O Phenyl

TABLE 76 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 1Bond (2-Cl,4-OMe)Phenyl NHCO(4) 0 Bond (1-Me)imidazo12-yl NHCO(4) 1 Bond(2,4-Cl)Phenyl NHCO(4) 1 Bond (2-Cl,4-OH)Phenyl NHCO(4) 1 Bond pyridin3-yl NHCO(4) 0 Bond Benzimidazol 2-yl NHCO(4) 0 Bond (2-Cl)PhenylNHCO(4) 0 Bond (2-Br)Phenyl NHCO(4) 0 Bond (2-I)Phenyl NHCO(4) 1 Bond(2-Me)Phenyl NHCO(4) 0 Bond Quinoxalin 2-yl NHCO(4) 0 Bond(5-Me)thiophen 2-yl NHCO(3) 1 Bond (2-Cl)Phenyl NHCO(4) 0 Bond(2,4,6-Me)Phenyl NHCO(4) 0 Bond (2-Et)Phenyl NHC(═S)NH(4) 0 Bond(2-Me)Phenyl

TABLE 77 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 0Bond (4-NMe₂)Phenyl NHCO(4) 1 ◯ (2,4-Cl)Phenyl NHCO(4) 1 ◯ (2-Me)PhenylNHCO(4) 0 Bond (2-Ac)Phenyl NHCO(4) 0 Bond (2-tBu)Phenyl NHCO(3) 0 Bond(2-I)Phenyl NHCO(4) 0 Bond (1-Me)piperdin 4-yl NHCO(4) 0 Bond benzofuran2-y1 NHCO(4) 0 Bond (1-Me)indol 3-y1 NHCO(4) 0 Bond (2-allyl)PhenylNHCO(4) 0 Bond (2-nPr)Phenyl NHCO(4) 0 Bond (2-iPrO)Phenyl NHCO(4) 0Bond 3-Me thiophen 2-yl NHCO(4) 1 ◯ (2-Me,3-Cl)Phenyl NHCO(4) 0 Bond(2-CF₃,4-F)Phenyl NHCO(4) 0 Bond (2-OMe,4-F)Phenyl

TABLE 78 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 0Bond (2-OH,4-F)Phenyl NHCO(3) 1 Bond (2-I)Phenyl NHCO(4) 0 Bond(3-NMe₂)Phenyl NHCO(4) 0 Bond (2-OMe,4-I)Phenyl NHCO(4) 0 Bond(2-OMe,6-F)Phenyl NHCO(4) 0 Bond (2-OH,4-I)Phenyl NHCO(4) 0 Bond(2-OH,6-F)Phenyl NHCO(4) 0 Bond (2-F)Phenyl NHCO(4) 0 Bond(2-NMe₂)Phenyl NHCO(4) 0 Bond (2-OMe,6-Me)Phenyl NHCO(4) 0 Bond(2-OH,6-Me)Phenyl NHCO(4) 2 Bond (2-Me)Phenyl CONH(4) 0 Bond PhenylCONH(4) 1 Bond Phenyl NHCO(4) 2 Bond (2-Cl)Phenyl CONH(4) 1 Bond(2-Cl)Phenyl

TABLE 79 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) CONH(4) 0Bond (2-Cl)Phenyl NHCO(4) 0 Bond (5-Br,2,3-methylenedioxy)Phenyl NHCO(4)0 Bond (2-OMe,6-Br)Phenyl NHCO(4) 0 Bond (2-OH,6-Br)Phenyl NHCO(4) 0Bond (2-OMe,6-Cl)Phenyl NHCO(4) 0 Bond (2-OH,6-Cl)Phenyl NHCO(4) 0 Bond(2-OH,6-OMe)Phenyl NHCO(4) 0 Bond (2-OMe,6-CF₃)Phenyl NHCO(4) 0 Bond(2-OH,6-CF₃)Phenyl NHCO(4) 0 Bond (2-Cl,5-SMe)Phenyl NHCO(4) 0 Bond(2-SMe)Phenyl NHCO(4) 0 Bond (3-SMe)Phenyl NHCO(4) 0 Bond(2-OMe,6-Et)Phenyl NHCO(4) 0 Bond (3-SO₂Me)Phenyl NHCO(4) 0 Bond(2-OH,6-Et)Phenyl NHCO(4) 0 Bond (3-S(═O)Me)Phenyl

TABLE 80 B^(Fa) (Substitution position) n^(F) E^(Fa) E^(Fa) NHCO(4) 0Bond (2-Cl,5-S(═O)Me)Phenyl NHCO(4) 0 Bond (2-S(═O)Me)Phenyl NHCO(4) 0Bond (3-Cl)pyridin 2-yl NHCO(4) 0 Bond (2-OMe,3-Cl)Phenyl NHCO(4) 0 Bond(3-Me)pyridin 2-yl NHCO(4) 0 Bond (2-OH,3-Cl)Phenyl NHCO(4) 0 Bond(3-OH)pyridin 2-yl NHCO(4) 0 Bond (3-Vinyl)pyridin 2-yl NHCO(4) 0 Bond(2-Et)pyridin2-yl NHSO₂(4) 0 Bond (2-NO₂)Phenyl NHSO₂(4) 0 Bond PhenylNHSO₂(4) 0 Bond (3-Br)Phenyl NHSO₂(4) 0 Bond (3-OMe)Phenyl NHSO₂(3) 0Bond (2-NO₂)Phenyl NMeSO₂(3) 0 Bond (2-NO₂)Phenyl NHSO₂(3) 0 Bondnaphthalen 2-yl

TABLE 81 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHSO₂(3) 0Bond naphthalen 1-yl NHSO₂(4) 0 Bond Cyclohexyl NHSO₂(4) 0 Bond pyridin3-yl NHSO₂(4) 0 Bond (4-iPr)Phenyl NHSO₂(4) 1 Bond Phenyl NHSO₂(4) 0Bond thiophen 2-yl NHSO₂(4) 0 Bond naphthalen 2-yl NBnSO₂(4) 0 Bond(2-NO₂)Phenyl NMeSO₂(4) 0 Bond (3-Br)Phenyl NMeSO₂(4) 0 Bond(2-NO₂)Phenyl N(CH₂CH₂OH) 0 Bond (2-NO₂)Phenyl SO₂(4) NHSO₂(4) 1 Bond(2-Cl)Phenyl NHSO₂(4) 1 Bond (3-Br)Phenyl NHSO₂(4) 0 Bond (2-CF₃)PhenylNHSO₂(4) 1 Bond (2-Br)Phenyl NHSO₂(4) 1 Bond (2-Me)Phenyl

TABLE 82 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHSO₂(4) 1Bond (2-NO₂)Phenyl NHSO₂(4) 2 Bond Phenyl NHSO₂(4) 1 Bond (4-Cl)PhenylNMeSO₂(4) 1 Bond (2-CF₃)Phenyl NMeSO₂(4) 1 Bond (2-Et)Phenyl NMeSO₂(4) 1Bond (2,3-Me)Phenyl NMeSO₂(4) 2 Bond (2-Cl)Phenyl NMeSO₂(4) 1 Bond(2-NO₂)Phenyl NMeSO₂(4) 1 Bond (2-NH₂)Phenyl NMeSO₂(4) 1 Bond(2-NMe₂)Phenyl

TABLE 83 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 0Bond pyridin 4-yl NHCO(4) 1 ◯ pyridin 3-yl NHCO(4) 0 Bond pyridin 3-ylNHCO(4) 0 Bond (2-Me)pyridin 3-yl NHCO(4) 0 Bond (2-Cl)pyridin 3-ylNHCO(4) 1 ◯ pyridin 2-yl NHCO(4) 0 Bond (4-CF₃)pyridin 3-yl NHCO(4) 0Bond (2-iPr)Phenyl

<Representative Compound F-200>

wherein B^(Fa) (substitution position), n^(F), E^(Fa), and G^(Fa) are asdescribed in Tables 84 and 85.

TABLE 84 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 0Bond Cyclohexyl NHCO(4) 0 Bond (6-Me)pyridin-2-yl NHCO(4) 0 Bond(2-Me)pyridin-3-yl NHCO(4) 0 Bond (2-OMe,3-Me)Phenyl NHCO(4) 0 Bond(2,3-Cl)Phenyl NHCO(4) 0 Bond (2-OH,3-Me)Phenyl NHCO(4) 0 Bond(2-I)Phenyl NHCO(4) 1 Bond (1-Me)pyrrol 2-yl NHCO(4) 1 Bond(2-tBu)Phenyl NHCO(4) 0 Bond (2-Isopropenyl)phenyl NHCO(4) 0 Bond(2-iPr)Phenyl NHCO(4) 1 Bond morpholin 2-yl NHCO(4) 0 Bond (2-Cl)pyridin2-yl

TABLE 85 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHSO₂(4) 0Bond (2-NO₂)Phenyl NMeSO₂(4) 0 Bond (2-NO₂)Phenyl SO₂NH(4) 0 Bond PhenylOSO₂(4) 0 Bond (3-Br)Phenyl NHSO₂(4) 1 Bond (2-Cl)Phenyl NHSO₂(4) 0 Bond(3-Br)Phenyl NHSO₂(4) 0 Bond (3-OMe)Phenyl NHSO₂(4) 1 Bond(2,3-Cl)Phenyl NHSO₂(4) 1 Bond (2,6-Cl)Phenyl NHSO₂(4) 1 Bond(2-I)Phenyl NMeSO₂(4) 1 Bond (2-Cl)Phenyl

<Representative Compound F-300>

wherein R^(1F), B^(Fa) (substitution position), n^(F), E^(Fa), andG^(Fa) are as described in Table 86.

TABLE 86 B^(Fa) (Substitution R¹ position) n^(F) E^(Fa) G^(Fa) 7-OMeNHCO(4) 0 Bond (2,3-Me)Phenyl 7-OH NHCO(4) 0 Bond (2,3-Me)Phenyl 6-MeNHCO(4) 0 Bond (2,3-Me)Phenyl 6,7-Me KHCO(4) 0 Bond (2-I)Phenyl 6-EtNHCO(4) 0 Bond (2-I)Phenyl 7-Ph NHCO(4) 0 Bond (2-Isopropyl))Phenyl7-(Pyridin- NHCO(4) 0 Bond (2-Isopropyl))Phenyl 3yl) 7-(Pyridin- NHCO(4)0 Bond (2-Isopropyl)Phenyl 2yl) 7-Cl NHSO₂(4) 0 Bond (2-Isopropyl)Phenyl7-Br NHSO₂(4) 0 Bond (2-Isopropyl)Phenyl 7-CF₃ MHSO₂(4) 0 Bond(2-Isopropyl)Phenyl H NHSO₂(4) 0 Bond (2-Isopropyl)Phenyl 6-Me,7-BrNHSO₂(4) 0 Bond (2-Isopropyl)Phenyl 7-OMe NHSO₂(4) 1 Bond (2-Cl)Phenyl7-OH NHSO₂(4) 1 Bond (2-Cl)Phenyl 6-Me NHSO₂(4) 1 Bond (2-Cl)Phenyl

<Representative Compound F-400>

wherein B^(Fa) (substitution position), n^(F), E^(Fa), and G^(Fa) are asdescribed in Table 87.

TABLE 87 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO 0 Bond(2-Cl,3-OMe)Phenyl NHCO 0 Bond (2-I)Phenyl NHSO₂ 1 Bond (2-Cl)PhenylNHSO₂ 1 Bond (2-Cl)Phenyl

<Representative Compound F-500>

wherein B^(Fa) (substitution position), n^(F), E^(Fa), and G^(Fa) are asdescribed in Table 88.

TABLE 88 B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa) NHCO(4) 0Bond (2-Cl,3-OMe)Phenyl NHCO(4) 0 Bond (2-Cl,3-OH)Phenyl NHCO(4) 0 Bond(2-tBu)Phenyl NHCO(4) 0 Bond (2-Cl,6-OMe)Phenyl NHCO(4) 0 Bond(2-Cl,6-OH)Phenyl NHSO₂(3) 0 Bond Phenyl NHSO₂(4) 1 Bond (2-Cl)Phenyl

<Representative Compound F-600>

wherein B^(F) (substitution position), D^(F), E^(F), and G^(F) are asdescribed in Table 89.

TABLE 89 B^(F) (Substitution Position) D^(F) E^(F) G^(F) NHCO(4) C(Me)HBond Phenyl NHCO(4) C(Me)₂ Bond Phenyl NHCO(4) CH═CH Bond Phenyl NHCO(4)C(Me)H ◯ Phenyl NHCO(4) C(Me)₂ ◯ Phenyl NHCO(4) CH═CH Bond (2-Me)PhenylNHCO(4) CH═CH Bond (2-Cl)Phenyl

<Representative Compound F-700>

wherein m^(F) (substitution position), B^(F), D^(F), E^(F), and G^(F)are as described in Table 90.

TABLE 90 m^(F) (Position) B^(F) D^(F) E^(F) G^(F) 1(4) NHCO Bond BondPhenyl 1(4) NHCO Bond Bond (2-Cl)Phenyl 1(4) NHSO₂ CH₂ Bond (2-Cl)Phenyl

<Representative Compound F-800>

wherein X^(Fa), Y^(Fa), B^(Fa) (substitution position), n^(F), E^(Fa),and G^(Fa) are as described in Table 91.

TABLE 91 B^(Fa) (Substitution X^(Fa) Y^(Fa) position) n^(F) E^(Fa)G^(Fa) CH C—F NHCO(4) 0 Bond (2,3-Me)Phenyl CH C—OH NHCO(4) 0 Bond(2,3-Me)Phenyl CH C—F NHCO(4) 0 Bond (2-I)Phenyl CH N NHCO(4) 0 Bond(2-I)Phenyl CH N NHCO(4) 0 Bond Phenyl N CH NHCO(4) 0 Bond (2-I)PhenylCH N NHCO(4) 0 Bond (2-Cl)Phenyl CH N NHCO(4) 0 Bond (2-OH)Phenyl CH NNHC(═O)NH(4) 0 Bond (2-OH)Phenyl CH N NHCO(4) 0 Bond (2-OH,6-Me)PhenylCH N NHCO(4) 0 Bond (2-OH,6-Cl)Phenyl CH N NHCO(3) 0 Bond(2-OH,6-Cl)Phenyl CH N NHCO(4) 0 Bond (2-Cl)pyridin 2-yl CH N NHCO(4) 1Bond (2-Cl)pyridin 2-yl CH N NHCO(4) 0 Bond (2-Me)pyridin 2-yl CH C—OMeNHSO₂(4) 1 Bond (2-Cl)Phenyl CH C—OH NHSO₂(4) 1 Bond (2-Cl)Phenyl

<Representative Compound F-900>

wherein I=II-III=IV, B^(Fa) (substitution position), n^(F), E^(Fa), andG^(Fa) are as described in Table 92.

TABLE 92 B^(Fa) (Substitution I═II—III═IV position) n^(F) E^(Fa) G^(Fa)N═CH—CH═CH NHCO(4) 0 Bond (2-I)Phenyl CH═N—CH═CH NHCO(4) 0 Bond(2-I)Phenyl CH═CH—N═CH NHCO(4) 0 Bond (2-I)Phenyl CH═CH—CH═N NHCO(4) 0Bond (2-I)Phenyl N═CH—CH═CH NHCO(4) 1 O Phenyl N═CH—CH═CH NHCO(3) 0 Bond(2-I)Phenyl N═CH—CH═CH NHCO(4) 0 Bond (2-Cl)Phenyl N═CH—CH═CH NHCO(4) 0Bond (2-OH)Phenyl N═CH—CH═CH NHC(═O)NH(4) 0 Bond (2-OH)Phenyl N═CH—CH═CHNHCO(4) 1 O (2-OH, 6-Me)Phenyl N═CH—CH═CH NHCO(4) 0 Bond (2-OH,6-Cl)Phenyl N═CH—CH═CH NHCO(3) 0 Bond (2-OH, 6-Cl)Phenyl N═CH—CH═CHNHCO(4) 0 Bond (2-Cl)pyridin 2-yl N═CH—CH═CH NHCO(4) 1 Bond(2-Cl)pyridin 2-yl N═CH—CH═CH NHCO(4) 0 Bond (2-Me)pyridin 2-ylCH═CH—N═CH NHCO(4) 0 Bond (2-Cl)pyridin 3-yl

<Representative Compound F-1000>

wherein I-II-III-IV, B^(Fa) (substitution position), n^(F), E^(Fa), andG^(Fa) are as described in Table 93.

TABLE 93 I—II—III—IV B^(Fa) (Substitution position) n^(F) E^(Fa) G^(Fa)NH—CH2—CH2—CH2 NHCO(4) 0 Bond (2-I)Phenyl CH2—NH—CH2—CH2 NHCO(4) 0 Bond(2-I)Phenyl CH2—CH2—NH—CH2 NHCO(4) 0 Bond (2-I)Phenyl CH2—CH2—CH2—NHNHCO(4) 0 Bond (2-I)Phenyl CH2—CH2—NH—CH2 NHCO(4) 1 O PhenylCH2—CH2—NH—CH2 NHCO(3) 0 Bond (2-I)Phenyl CH2—CH2—NH—CH2 NHCO(4) 0 Bond(2-Cl)Phenyl CH2—CH2—NH—CH2 NHCO(4) 0 Bond (2-Cl)pyridin 3-ylCH2—CH2—NH—CH2 NHCO(4) 0 Bond (2-OH)Phenyl CH2—CH2—NH—CH2 NHC(═O)NH(4) 0Bond (2-OH)Phenyl CH2—CH2—NH—CH2 NHCO(4) 1 O (2-OH, 6-Me)PhenylCH2—CH2—NH—CH2 NHCO(4) 0 Bond (2-OH, 6-Cl)Phenyl CH2—CH2—NH—CH2 NHCO(3)0 Bond (2-OH, 6-Cl)Phenyl CH2—CH2—NH—CH2 NHCO(4) 0 Bond (2-Cl)pyridin2-yl CH2—CH2—NH—CH2 NHCO(4) 1 Bond (2-Cl)pyridin 2-yl CH2—CH2—NH—CH2NHCO(4) 0 Bond (2-Me)pyridin 2-yl CH2—CH2—NH—CH2 NHCO(4) 0 Bond(2-Cl)pyridln 3-y

<Representative Compound F-1100>

wherein R^(5Fa), B^(Fa) (substitution position), n^(F), E^(Fa), andG^(Fa) are as described in Table 94.

TABLE 94 B^(Fa) (Substitution R^(5Fa) position) n^(F) E^(Fa) G^(Fa) BnNBnSO₂(4) 0 Bond (2-NO₂)Phenyl Me NBnSO₂(4) 0 Bond (2-NO₂)Phenyl EtNBnSO₂(4) 0 Bond (2-NO₂)Phenyl

(G-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (GI):

wherein R^(1G), R^(2G), and R^(3G) are the same or different andrepresent a hydrogen atom, a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group,a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group,

X^(G) represents C or N,

Y^(G) represents N or C(═O),

provided that when X^(G) is C, Y^(G) represents N, and

when X^(G) is N, Y^(G) represents C(═O)

a double line composed of a solid line and a dashed line denotes asingle bond or a double bond,

n^(G) represents an integer of 0 to 6,

Z^(G) represents O, S, or a bond, and

A^(G) represents a benzene ring, a pyridine ring, a piperazine ring, apiperidine ring, or a morpholine ring optionally having, assubstituents, 1 to 5 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, or N(R^(4G))(R^(5G))where R^(4G) and R^(5G) are the same or different and represent a C₁₋₈alkyl group or R^(4G) and R^(5G) and a nitrogen atom bonded to R^(4G)and R^(5G) are fused to represent a 5- to 7-membered ring furtheroptionally comprising, as a ring forming atom, an oxygen atom or asulfur atom as a heteroatom.

Examples of the C₁₋₈ alkyl group in general formula (GI) include amethyl, ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl, orhexyl group.

Examples of the C₃₋₈ cycloalkyl group include a cyclopropyl group or acyclohexyl group.

Examples of the C₂₋₈ alkenyl group include an allyl group.

Examples of the C₁₋₈ alkoxy group include a methoxy, ethoxy, propoxy,isopropoxy, butoxy, i-butoxy, t-butoxy, pentyloxy, or hexyloxy group.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsinclude a methyl, ethyl, propyl, isopropyl, butyl, or t-butyl groupsubstituted with 1 to 3 halogen atoms such as fluorine, chlorine, orbromine atoms, and preferably a trifluoromethyl, chloromethyl,2-chloroethyl, 2-bromoethyl, or 2-fluoroethyl group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsinclude a methoxy, ethoxy, propoxy, isopropoxy, butoxy, or t-butoxygroup substituted with 1 to 3 halogen atoms such as fluorine, chlorine,or bromine atoms, and preferably a trifluoromethoxy, chloromethoxy,2-chloroethoxy, 2-bromoethoxy, or 2-fluoroethoxy group.

Examples of the halogen atom include a fluorine, chlorine, or bromineatom.

Examples of the C₁₋₈ alkylamino group include a methylamino orethylamino group.

Examples of the C₂₋₈ dialkylamino group include a dimethylamino ordiethylamino group.

Examples of the 5- to 7-membered ring together formed by fusing R^(4G)and R^(5G) and a nitrogen atom bonded to R^(4G) and R^(5G) andoptionally further comprising, as a ring forming atom, an oxygen atom ora sulfur atom as a heteroatom include morpholin-4-yl, 1H-pyrrol-1-yl, orpyrrolidin-1-yl.

In the above R^(1G), 1 to 4 substituents, which are the same ordifferent, may be present.

In the above R^(2G), 1 to 2 substituents, which are the same ordifferent, may be present.

In the above R^(3G), 1 to 4 substituents, which are the same ordifferent, may be present.

The following compounds are preferable as compounds represented bygeneral formula (GI).

(G-1-1)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1), wherein A^(G) is a benzene ring, a pyridine ring,a piperazine ring, a piperidine ring, or a morpholine ring optionallyhaving, as substituents, 1 to 5 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group, aC₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylaminogroup.

(G-1-2)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1), wherein A^(G) is a benzene ring or a pyridine ringoptionally having, as substituents, 1 to 5 substituents, which are thesame or different, selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group.

(G-1-3)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1), wherein A^(G) is a benzene ring optionally having,as substituents, 1 to 5 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a halogen atom, ahydroxyl group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group.

(G-1-4)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1), wherein where A^(G) is a pyridine ring havingN(R^(4G))(R^(5G)) (where regarding R^(4G) and R^(5G), R^(4G) and R^(5G)and a nitrogen atom bonded to R^(4G) and R^(5G) are fused to represent a5- to 7-membered ring further optionally comprising, as a ring formingatom, an oxygen atom or a sulfur atom as a heteroatom).

(G-1-5)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1), wherein where A^(G) is a pyridine ring optionallyhaving, as a substituent, a substituent selected from morpholin-4-yl,1H-pyrrol-1-yl, or pyrrolidin-1-yl.

(G-1-6)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1) or the compound represented by any of (G-1-1) to(G-1-5), wherein R^(1G), R^(2G), and R^(3G) are the same or differentand are a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, or a halogen atom.

(G-1-7)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1) or the compound represented by any of (G-1-1) to(G-1-5), wherein R^(1G), R^(2G), and R^(3G) are the same or differentand are a hydrogen atom or a halogen atom.

(G-1-8)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1) or the compound represented by any of (G-1-1) to(G-1-7), wherein n^(G) is 0.

(G-1-9)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1) or the compound represented by any of (G-1-1) to(G-1-7), wherein n^(G) is 1 or 2.

(G-1-10)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1) or the compound represented by any of (G-1-1) to(G-1-9), wherein Z^(G) is a bond.

(G-1-11)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1), wherein R^(1G), R^(2G), and R^(3G) are the same ordifferent and are a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, or ahydroxyl group,

X^(G) is N,

Y^(G) is C(═O),

the double line composed of a solid line and a dashed line denotes asingle bond,

n^(G) is 0,

Z^(G) is a bond, and

A^(G) is a benzene ring or a pyridine ring optionally having, assubstituents, 1 to 3 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,an amino group, a C₁₋₈ alkylamino group, or N(R^(4G))(R^(5G)) whereR^(4G) and R^(5G) are the same or different and represent a C₁₋₈ alkylgroup or R^(4G) and R^(5G) and a nitrogen atom bonded to R^(4G) andR^(5G) are fused to represent a morpholine ring, a pyrrole ring, or apyrrolidine ring.

(G-1-12)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1), wherein R^(1G), R^(2G), and R^(3G) are the same ordifferent and represent a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, or a hydroxyl group,

X^(G) is C,

Y^(G) is N,

the double line composed of a solid line and a dashed line denotes adouble bond,

n^(G) is an integer of 0 to 3,

Z^(G) is a bond, and

A^(G) represents a benzene ring or a pyridine ring optionally having, assubstituents, 1 to 3 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,an amino group, a C₁₋₈ alkylamino group, or N(R^(4G))(R^(5G)) whereR^(4G) and R^(5G) are the same or different and represent a C₁₋₈ alkylgroup or R^(4G) and R^(5G) and a nitrogen atom bonded to R^(4G) andR^(5G) are fused to represent morpholine, a pyrrole ring, or apyrrolidine ring.

(G-1-13)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (G-1) or the compound represented by any of (G-1-1) to(G-1-12), wherein X^(G) and NHC(═O) are at para positions of a phenylgroup.

In the above general formula (GI), it is preferable that R^(1G), R^(2G),and R^(3G) are a hydrogen atom.

In the above general formula (GI), it is preferable that X^(G) is C,Y^(G) is N, and the double line composed of a solid line and a dashedline is a double bond.

In the above general formula (GI), it is preferable that n^(G) is 0.

In the above general formula (GI), it is preferable that Z^(G) is abond.

In the above general formula (GI), it is preferable that A^(G)represents a pyridine ring optionally having, as substituents, 1 to 3substituents, which are the same or different, selected fromN(R^(4G))(R^(5G)) where R^(4G) and R^(5G) are the same or different andrepresent a C₁₋₈ alkyl group. It is more preferable that A^(G) is apyridine ring having, as a substituent, a C₁₋₈ dialkylamino group. It issuitable that A^(G) is a pyridine ring having, as a substituent, adimethylamino group.

In the above general formula (GI), it is preferable that R^(1G), R^(2G),and R^(3G) are a hydrogen atom, X^(G) is C, Y^(G) is N, the double linecomposed of a solid line and a dashed line is a double bond, n^(G) is 0,Z^(G) is a bond, and A^(G) is a pyridine ring having, as a substituent,a C₁₋₈ dialkylamino group. It is suitable that A^(G) is a pyridine ringhaving, as a substituent, a dimethylamino group.

In the above general formula (GI), it is preferable that R^(1G), R^(2G),and R^(3G) are a hydrogen atom, X^(G) is N, Y^(G) is C(═O), the doubleline composed of a solid line and a dashed line is a single bond, n^(G)is 0, Z^(G) is a bond, A^(G) is a pyridine ring having, as asubstituent, a C₁₋₈ dialkylamino group. It is suitable that A^(G) is apyridine ring having, as a substituent, a dimethylamino group.

The following shows representative compounds included in general formula(GI).

<Representative Compound G-100>

wherein R^(3G), A^(G), Z^(G), and n^(G) are as described in Tables 95and 96.

TABLE 95 R^(3G) n^(G) Z^(G) A^(G) H 2 Bond Pyridin 2-yl H 0 Bond (2-Et,3-OH)Phenyl H 0 Bond (2-Et)Pyridin 3-yl H 0 Bond (2-Et, 6-OH)Phenyl H 0Bond (3-Et)Pyridin 2-yl H 1 O Pyridin 2-yl H 1 Bond (2-OMe)Phenyl H 2Bond Pyridin 3-yl H 2 Bond Phenyl H 2 Bond Cyclohexyl H 1 Bond Pyridin2-yl

TABLE 96 R^(3G) n^(G) Z^(G) A^(G) H 1 Bond Pyridin 3-yl H 1 Bond Pyridin4-yl H 3 Bond Pyridin 2-yl H 1 Bond (2-NMe₂)Phenyl OH 1 O Pyridin 2-ylOMe 2 O Pyridin 2-yl CN 2 Bond Pyridin 2-yl Me 2 Bond Pyridin 2-yl CF₃ 1Bond Pyridin 2-yl F 2 Bond Pyridin 2-yl H 0 Bond (2-NMe₂) pyridin 3-yl F2 Bond Phenyl

<Representative Compound G-200>

wherein R^(3G), A^(G), Z^(G), and n^(G) are as described in Tables 97and 98.

TABLE 97 R^(3G) n^(G) Z^(G) A^(G) H 2 Bond Pyridin 3-yl H 2 Bond Pyridin4-yl F 0 Bond (2-t Bu)phenyl H 2 Bond Pyridin 2-yl H 0 Bond(2-NMe₂)pyridin 3-yl H 2 Bond Cyclohexyl H 1 Bond Pyridin 2-yl H 1 BondPyridin 3-yl

TABLE 98 R^(3G) n^(G) Z^(G) A^(G) H 1 Bond Pyridin 4-yl H 3 Bond Pyridin2-yl H 1 Bond (2-NMe2)Phenyl OH 1 O Pyridin 2-yl OMe 2 O Pyridin 2-yl CN2 Bond Pyridin 2-yl Me 2 Bond Pyridin 2-yl CF3 1 Bond Pyridin 2-yl F 2Bond Pyridin 2-yl F 2 Bond Phenyl

<Representative Compound G-300>

wherein R^(1G), R^(2G), and the salt are as described in Tables 99 and100.

TABLE 99 R^(1G) R^(2G) Salt H NMe₂ 2HCl H NMe₂ 2MsOH H 1H-pyrrol-1-yl2HCl H morpholin-4-yl 2HCl H pyrrolidin-1-yl 2HCl H iPr 2HCl H iPrNH2HCl F NMe₂ OH HMe₂ F 1H-pyrrol-1-yl OH morpholin-4-yl

TABLE 100 R^(1G) R^(2G) Salt F pyrrolidin-1-yl OH iPr F iPrNH H NEt₂ HNHEt F NHMe Me 1H-pyrrol-1-yl Me morpholin-4-yl Me pyrrolidin-1-yl

<Representative Compound G-400>

wherein R^(1G), R^(2G), and the salt are as described in Table 101.

TABLE 101 R^(1G) R^(2G) Salt H MMe₂ 2HCl H 1H-pyrrol-1-yl Hmorpholin-4-yl H pyrroidin-1-yl H iPr H iPrNH F NMe₂

<Representative Compound G-500>

wherein R^(1G), R^(2G), and the salt are as described in Table 102.

TABLE 102 R^(1G) R^(2G) Salt H NMe₂ HCl H morpholin-4-yl HCl Hpyrrolidin-1-yl H iPr H iPrNH F NMe₂ OH NMe₂ F 1H-pyrrol-1-yl OHmorpholin-4-yl F pyrrolidin-1-yl OH iPr F iPrNH H NEt₂ H NHEt F NHMe Me1H-pyrrol-1-yl Me morpholin-4-yl

(H-1) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (HI):

wherein R^(1H) and R^(2H) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), an optionally substituted phenyl group, an optionallysubstituted pyridyl group, or an aralkyl group (the number of carbonatoms in an aryl moiety is from 6 to 10 and the number of carbon atomsin an alkylene moiety is from 1 to 8), or

R^(1H) and R^(2H) are optionally fused with a benzene ring bondedthereto to form a condensed ring selected from a naphthalene ring, aquinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, anindane ring, a tetrahydroquinoline ring, or a tetrahydroisoquinolinering and a ring fused with R^(1H) and R^(2H) and comprising carbon atomsbonded to respective R^(1H) and R^(2H) is optionally substituted with 1to 4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),

R^(3H) and R^(4H) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, a nitro group, a cyano group, an amino group, a C₁₋₈ alkylaminogroup, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxylgroup, a C₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbonatoms in an alkoxy moiety is from 1 to 8), or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8),

R^(5H) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, ahydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (the numberof carbon atoms in an aryl moiety is from 6 to 10 and the number ofcarbon atoms in an alkylene moiety is from 1 to 8),

R^(6H) and R^(7H) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, or an amino group,

X^(H) represents C or N,

Y^(H) represents N or C(═O),

provided that when X^(H) is C, Y^(H) represents N, and

when X^(H) is N, Y^(H) represents C(═O)

a double line composed of a solid line and a dashed line denotes asingle bond or a double bond,

Z^(H) represents O, S, or NH,

A^(H) represents a benzene ring, a pyridine ring, a pyrimidine ring, apyridazine ring, a thiophene ring, a furan ring, a pyrazole ring, animidazole ring, a quinoline ring, a benzimidazole ring, or an indanering optionally having, as substituents, 1 to 4 substituents, which arethe same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group,

B^(H) represents O, S, NR^(8H), or a bond,

R^(8H) here represents a hydrogen atom or a C₁₋₈ alkyl group,

D^(H) represents a benzene ring, a pyridine ring, a pyrimidine ring, apyridazine ring, a thiophene ring, a furan ring, a tetrazole ring, animidazole ring, an imidazoline ring, a triazole ring, a thiazole ring,an oxazole ring, an isoxazole ring, a pyrazole ring, a pyrrole ring, apyrrolidine ring, a piperazine ring, a piperidine ring, or a 5- to8-membered cycloalkyl ring optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group,or a C₂₋₈ dialkylamino group,

EH represents —(CR^(9H)R^(10H))_(n) ^(H)-T-,

R^(9H) and R^(10H) here are the same or different and represent ahydrogen atom, a hydroxyl group, or a C₁₋₈ alkyl group, or R^(9H) andR^(10H) are optionally fused to form an ethylene chain,

n^(H) represents an integer of 0 to 8,

T^(H) represents O, S, NR^(11H), or a bond,

R^(11H) here represents a hydrogen atom or a C₁₋₈ alkyl group,

G^(H) represents a benzene ring, a pyridine ring, an imidazole ring, apyrrole ring, a pyrazole ring, a thiophene ring, a furan ring, athiazole ring, an oxazole ring, a pyrimidine ring, a pyridazine ring, apyrazine ring, a naphthalene ring, a quinoline ring, a quinazoline ring,an indole ring, an indoline ring, a piperazine ring, a piperidine ring,a morpholine ring, or a 5- to 8-membered cycloalkyl ring optionallyhaving, as substituents, 1 to 5 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a carbamoylgroup, or a methanesulfonyl group, and

m^(H) represents an integer of 0 to 2.

(H-2) A compound, a tautomer, stereoisomer, or pharmaceuticallyacceptable salt of the compound, or a hydrate or solvate thereof, thecompound represented by the following general formula (HII):

wherein R^(1Ha), R^(2Ha), R^(3Ha), R^(4Ha), R^(5Ha), and R⁶Ha are thesame or different and represent a hydrogen atom, a C₁₋₈ alkyl group, aC₃₋₈ cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxyl group, aC₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbon atoms inan alkoxy moiety is from 1 to 8), an optionally substituted phenylgroup, an optionally substituted pyridyl group, or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8),

X^(Ha) represents C or N,

Y^(Ha) represents N or C(═O),

provided that when X^(Ha) is C, Y^(Ha) represents N, and

when X^(Ha) is N, Y^(Ha) represents C(═O),

a double line composed of a solid line and a dashed line denotes asingle bond or a double bond,

A^(Ha) represents a benzene ring, a pyridine ring, a pyrimidine ring, apyridazine ring, a thiophene ring, a furan ring, a pyrazole ring, animidazole ring, a quinoline ring, a benzimidazole ring, or an indanering optionally having, as substituents, 1 to 4 substituents, which arethe same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group,

D^(Ha) represents a benzene ring, a pyridine ring, a pyrimidine ring, apyridazine ring, a thiophene ring, a furan ring, a tetrazole ring, animidazole ring, an imidazoline ring, a triazole ring, a thiazole ring,an oxazole ring, an isoxazole ring, a pyrazole ring, a pyrrole ring, apyrrolidine ring, a piperazine ring, a piperidine ring, or a 5- to8-membered cycloalkyl ring optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group,or a C₂₋₈ dialkylamino group,

E^(Ha) represents —(CR^(9Ha)R^(10Ha))_(p)-T^(Ha)-,

R^(9Ha) and R^(10Ha) here are the same or different and represent ahydrogen atom, a hydroxyl group, or a C₁₋₈ alkyl group, or R^(9Ha) andR^(10Ha) are optionally fused to form an ethylene chain,

p represents an integer of 0 to 8,

T^(Ha) represents O, S, NR^(11Ha), or a bond,

R^(11Ha) here represents a hydrogen atom or a C₁₋₈ alkyl group, and

G^(Ha) represents a benzene ring, a pyridine ring, an imidazole ring, apyrrole ring, a pyrazole ring, a thiophene ring, a furan ring, athiazole ring, an oxazole ring, a pyrimidine ring, a pyridazine ring, apyrazine ring, a naphthalene ring, a quinoline ring, a quinazoline ring,an indole ring, an indoline ring, a piperazine ring, a piperidine ring,a morpholine ring, or a 5-to 8-membered cycloalkyl ring optionallyhaving, as substituents, 1 to 5 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a carbamoylgroup, or a methanesulfonyl group.

Next, the present invention will be described in detail.

As used herein, examples of the C₁₋₈ alkyl group include a methyl,ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl, or hexylgroup.

Examples of the 5- to 8-membered cycloalkyl ring include a cyclopentylring or a cyclohexyl ring.

Examples of the C₃₋₈ cycloalkyl group include a cyclopropyl group or acyclohexyl group.

Examples of the C₂₋₈ alkenyl group include an allyl group.

Examples of the C₁₋₈ alkoxy group include a methoxy, ethoxy, propoxy,isopropoxy, butoxy, i-butoxy, t-butoxy, pentyloxy, or hexyloxy group.

Examples of the C₁₋₈ alkyl group substituted with 1 to 3 halogen atomsinclude a methyl, ethyl, propyl, isopropyl, butyl, or t-butyl groupsubstituted with 1 to 3 halogen atoms such as fluorine, chlorine, orbromine atoms, and preferably a trifluoromethyl, chloromethyl,2-chloroethyl, 2-bromoethyl, or 2-fluoroethyl group.

Examples of the C₁₋₈ alkoxy group substituted with 1 to 3 halogen atomsinclude a methoxy, ethoxy, propoxy, isopropoxy, butoxy, or t-butoxygroup substituted with 1 to 3 halogen atoms such as fluorine, chlorine,or bromine atoms, and preferably a trifluoromethoxy, chloromethoxy,2-chloroethoxy, 2-bromoethoxy, or 2-fluoroethoxy group.

Examples of the halogen atom include a fluorine, chlorine, or bromineatom.

Examples of the C₁₋₈ alkylamino group include a methylamino orethylamino group.

Examples of the C₂₋₈ dialkylamino group include a dimethylamino ordiethylamino group.

Examples of the C₂₋₈ acylamino group include an acetylamino group.

Examples of the C₂₋₈ acyl group include an acetyl group.

Examples of the alkoxycarbonyl group (the number of carbon atoms in analkoxy moiety is from 1 to 8) include a methoxycarbonyl group.

Examples of the aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 8) include a benzyl group.

Examples of the hydroxyl-substituted C₁₋₈ alkyl group include2-hydroxyethyl group.

Examples of an optional substituent of the optionally substituted phenylgroup or the optionally substituted pyridyl group include a halogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, or a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms.

In E^(H) or E^(Ha) of general formula (HI) or (HII), the wording“R^(9Ha) and R^(10Ha) are optionally fused to form an ethylene chain”means that E^(H) or E^(Ha) optionally has a double bond.

The following compounds are preferable as present compounds representedby general formula (HI).

(H-1-1)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1), wherein m^(H) is 1.

(H-1-2)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or (H-1-1), wherein R^(1H) and R^(2H) are fusedwith a benzene ring bonded thereto to form a naphthalene ring and thenaphthalene ring optionally substituted with 1 to 4 substituents, whichare the same or different, selected from a C₁₋₈ alkyl group, a C₃₋₈cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group,or a C₂₋₈ dialkylamino group.

(H-1-3)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-2), wherein R^(3H) andR^(4H) are the same or different and are a hydrogen atom, a C₁₋₈ alkylgroup, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group.

(H-1-4)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-3), wherein R^(5H) is ahydrogen atom.

(H-1-5)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-4), wherein R^(6H) andR^(7H) are a hydrogen atom.

(H-1-6)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-5), wherein X^(H) is Nand Y^(H) is C(═O).

(H-1-7)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-6), wherein Z^(H) is O.

(H-1-8)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-7), wherein A^(H) is abenzene ring or a pyridine ring optionally having, as substituents, 1 to4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group,or a C₂₋₈ dialkylamino group.

(H-1-9)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-8), wherein D^(H) is atetrazole ring, an imidazole ring, an imidazoline ring, a triazole ring,a pyrrole ring, a pyrrolidine ring, a piperazine ring, or a piperidinering optionally having, as substituents, 1 to 4 substituents, which arethe same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group.

(H-1-10)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-9), wherein B^(H) is abond.

(H-1-11)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1-10), wherein D^(H) is bonded via a nitrogen atom toA.

(H-1-12)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-11), wherein E^(H) is aC_(Z)-5 alkylene chain.

(H-1-13)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1) or any of (H-1-1) to (H-1-12), wherein G^(H) is abenzene ring, a pyridine ring, an imidazole ring, a pyrrole ring, apyrazole ring, a pyrimidine ring, a pyridazine ring, a pyrazine ring, ora 5- to 7-membered cycloalkyl ring optionally having, as substituents, 1to 5 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a carbamoyl group, or a methanesulfonyl group.

(H-1-14)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1), wherein R^(1H) and R^(2H) are fused with a benzenering bonded thereto to form a naphthalene ring or an indane ring and

the naphthalene ring or indane ring is optionally substituted with 1 to4 substituents, which are the same or different, selected from a C₁₋₈ salkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),

R^(3H) and R^(4H) are the same or different and are a hydrogen atom, aC_(Z-8) alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxyl group, aC₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbon atoms inan alkoxy moiety is from 1 to 8), or an aralkyl group (the number ofcarbon atoms in an aryl moiety is from 6 to 10 and the number of carbonatoms in an alkylene moiety is from 1 to 8),

R^(5H) is a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, ahydroxyl-substituted C_(Z-s) alkyl group, or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8),

R^(6H) and R^(7H) are the same or different and are a hydrogen atom, aC₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,or an amino group,

X^(H) is N,

Y^(H) is C(═O),

the double line composed of a solid line and a dashed line is a singlebond,

Z^(H) is O,

A^(H) is a benzene ring or a pyridine ring optionally having, assubstituents, 1 to 4 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, or a C₂₋₈ dialkylamino group,

B is a bond,

D^(H) is a tetrazole ring or an imidazole ring optionally having, assubstituents, 1 to 2 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₁₋₈alkylamino group, or a C₂₋₈ dialkylamino group,

D^(H) is bonded via a nitrogen atom of D^(H) to A^(H) and via a carbonatom of D^(H) to E^(H),

E^(H) is —(CR^(9H)R^(10H))_(n)—,

R^(9H) and R^(10H) here are the same or different and are a hydrogenatom, a hydroxyl group, or a C₁₋₈ alkyl group,

n is an integer of 1 to 8,

G^(H) is a benzene ring optionally having, as substituents, 1 to 5substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a carbamoyl group, or a methanesulfonyl group,and

m is 1.

(H-1-15)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1), wherein R^(1H) and R^(2H) are fused with a benzenering bonded thereto to form a naphthalene ring or an indane ring,

R^(3H) and R^(4H) are a hydrogen atom,

R⁵H is a hydrogen atom,

R⁶H and R^(7H) are a hydrogen atom,

X^(H) is N,

Y^(H) is C(═O),

the double line composed of a solid line and a dashed line is a singlebond,

Z^(H) is O,

A^(H) is a benzene ring optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group,

B^(H) is a bond,

D^(H) is a tetrazole ring or an imidazole ring optionally having 1 to 2substituents selected from a C₁₋₈ alkyl group or a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms,

D^(H) is bonded via a nitrogen atom of D^(H) to A^(H) and via a carbonatom of D^(H) to E^(H),

E^(H) is —(CR^(9H)R^(10H))_(n)—,

R^(9H) and R^(10H) here are the same or different and are a hydrogenatom or a C₁₋₈ alkyl group,

n is an integer of 1 to 4,

G^(H) is a benzene ring optionally having, as substituents, 1 to 5substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, or acarbamoyl group, and

m^(H) is 1.

(H-1-16)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-1), wherein R^(1H) and R^(2H) are fused with a benzenering bonded thereto to form a naphthalene ring or an indane ring,

R^(3H) and R^(4H) are a hydrogen atom,

R^(5H) is a hydrogen atom,

R^(6H) and R^(7H) are a hydrogen atom,

X^(H) is N,

Y^(H) is C(═O),

the double line composed of a solid line and a dashed line is a singlebond,

Z^(H) is O,

A^(H) is a benzene ring optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group,

B^(H) is a bond,

D^(H) is an imidazole ring optionally having 1 to 2 substituentsselected from a C₁₋₈ alkyl group or a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms,

D^(H) is bonded at position 2 of the imidazole ring to A^(H) and via anitrogen atom of the imidazole to E^(H),

E^(H) is —(CR^(9H)R^(10H))_(n)—,

R^(9H) and R^(10H) here are the same or different and are a hydrogenatom or a C₁₋₈ alkyl group,

n is an integer of 1 to 4,

G^(H) is a benzene ring optionally having, as substituents, 1 to 5substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, or acarbamoyl group, and

m^(H) is 1.

(H-2-1)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2), wherein R^(1Ha), R^(2Ha), R^(3Ha), R^(4Ha),R^(5Ha), and R^(6Ha) are the same or different and are a hydrogen atom,a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, or a hydroxyl group.

(H-2-2)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or (H-2-1), wherein X^(Ha) is N and Y^(Ha) isC(═O).

(H-2-3)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or any of (H-2-1) to (H-2-2), wherein A^(Ha) is abenzene ring or a pyridine ring optionally having, as substituents, 1 to4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group,or a C₂₋₈ dialkylamino group.

(H-2-4)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or any of (H-2-1) to (H-2-3), wherein A^(Ha) is abenzene ring optionally having, as substituents, 1 to 4 substituents,which are the same or different, selected from a C₁₋₈ alkyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, or anamino group.

(H-2-4)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or any of (H-2-1) to (H-2-3), wherein D^(Ha) is atetrazole ring, an imidazole ring, an imidazoline ring, a triazole ring,a pyrrole ring, a pyrrolidine ring, a piperazine ring, or a piperidinering optionally having, as substituents, 1 to 4 substituents, which arethe same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group.

(H-2-5)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or any of (H-2-1) to (H-2-4), wherein D^(Ha) is atetrazole ring.

(H-2-6)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or any of (H-2-1) to (H-2-5), wherein D^(Ha) isbonded via a nitrogen atom to A^(Ha).

(H-2-7)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or any of (H-2-1) to (H-2-6), wherein E^(Ha) is aC₁₋₅ alkylene chain.

(H-2-8)

A compound, a tautomer, stereoisomer, or pharmaceutically acceptablesalt of the compound, or a hydrate or solvate thereof, the compoundrepresented by (H-2) or any of (H-2-1) to (H-2-7), wherein G^(Ha) is abenzene ring, a pyridine ring, an imidazole ring, a pyrrole ring, apyrazole ring, a pyrimidine ring, a pyridazine ring, a pyrazine ring, ora 5- to 7-membered cycloalkyl ring optionally having, as substituents, 1to 5 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a carbamoyl group, or a methanesulfonyl group.

In the above general formula (HI), it is preferable that when A^(H) isan optionally substituted benzene ring and B^(H) is a bond, X^(H) andD^(H) are at para positions of the benzene ring.

Also, in the above general formula (HI), it is preferable that whenA^(H) is an optionally substituted pyridine ring and B^(H) is a bond,A^(H) is bonded at position 3 of the pyridine ring to X^(H) and atposition 6 of the pyridine ring to D^(H).

Further, in the above general formula (HII), it is preferable that whenA^(Ha) is an optionally substituted benzene ring, X^(Ha) and D^(Ha) areat para positions of the benzene ring.

Furthermore, in the above general formula (HII), it is preferable thatwhen A^(Ha) is an optionally substituted pyridine ring, A^(Ha) is bondedat position 3 of the pyridine ring to X^(Ha) and at position 6 of thepyridine ring to D^(Ha).

In the above general formula (HI), it is preferable that R^(H1) andR^(H2) are fused with a benzene ring bonded thereto to form a condensedring selected from a naphthalene ring, a tetrahydronaphthalene ring, oran indane ring. It is particularly preferable to form a naphthalenering.

In the above general formula (HI), it is preferable that R^(H3), R^(H4),R^(H5), R^(H6), and R^(H7) represent a hydrogen atom.

In the above general formula (HI), it is preferable that X^(H)represents N, Y^(H) represents C(═O), the double line composed of asolid line and a dashed line denotes a single bond, and Z^(H) representsO.

In the above general formula (HI), it is preferable that A^(H)represents a benzene ring or a pyridine ring. It is particularlypreferable that A^(H) represents a benzene ring.

In the above general formula (HI), it is preferable that B^(H)represents a bond.

In the above general formula (HI), it is preferable that D^(H)represents a tetrazole ring or an imidazole ring.

In the above general formula (HI), it is preferable that E^(H)represents —(CR^(9H)R^(10H))_(n) ^(H)-T- where R^(9H) and R^(10H)represent a hydrogen atom, n^(H) represents an integer of 0 to 4, andT^(H) represents a bond. Among them, it is more preferable that n^(H)represents an integer of 1 or 2.

In the above general formula (HI), it is preferable that G^(H)represents a benzene ring or a thiophene ring optionally having, assubstituents, 1 to 5 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a halogen atom, ahydroxyl group, or a C₂₋₈ dialkylamino group. It is more preferable thatG^(H) represents a benzene ring or a thiophene ring optionally having,as substituents, 1 to 5 substituents, which are the same or different,selected from a C₁_₄ alkyl group, a C₁₋₄ alkoxy group, a halogen atom, ahydroxyl group, or a C₂₋₄ dialkylamino group. It is particularlypreferable that G^(H) represents a benzene ring optionally having, assubstituents, 1 to 5 substituents, which are the same or different,selected from a methyl group, a methoxy group, a halogen atom, ahydroxyl group, or a dimethylamino group.

In the above general formula (HI), it is preferable that R^(H1) andR^(H2) are fused with a benzene ring bonded thereto to form a condensedring selected from a naphthalene ring or an indane ring, R^(H3), R^(H4),R^(H5), R^(H6), and R^(H7) represent a hydrogen atom, X^(H) representsN, Y^(H) represents C(═O), the double line composed of a solid line anda dashed line represents a single bond, Z^(H) represents O, A^(H)represents a benzene ring or a pyridine ring, B^(H) represents a bond,D^(H) represents a tetrazole ring or an imidazole ring, E^(H) represents—(CR^(9H)R^(10H))_(n)-T-, R^(9H) and R^(10H) represent a hydrogen atom,n^(H) represents an integer of 0 to 4, T^(H) represents a bond, andG^(H) is a benzene ring or a thiophene ring optionally having, assubstituents, 1 to 5 substituents, which are the same or different,selected from a C₁₋₈ alkyl group, a C₁₋₈ alkoxy group, a halogen atom, ahydroxyl group, or a C₂₋₈ dialkylamino group.

In the above general formula (HI), it is particularly preferable thatR^(H1) and R^(H2) are fused with a benzene ring bonded thereto to form anaphthalene ring, R^(H3), R^(H4), R^(H5), R^(H6), and R^(H7) represent ahydrogen atom, X^(H) represents N, Y^(H) represents C(═O), the doubleline composed of a solid line and a dashed line represents a singlebond, Z^(H) represents O, A^(H) represents a benzene ring, B^(H)represents a bond, D^(H) represents a tetrazole ring or an imidazolering, E^(H) represents —(CR^(9H)R^(10H))_(n)-T-, R^(9H) and R^(10H)represent a hydrogen atom, n^(H) represents an integer of 1 or 2, T^(H)represents a bond, and G^(H) is a benzene ring optionally having, assubstituents, 1 to 5 substituents, which are the same or different,selected from a methyl group, a methoxy group, a halogen atom, ahydroxyl group, or a dimethylamino group.

<Representative Compound H-100>

wherein R^(Hc), E^(H), and G^(H) are as described in Tables 103 to 105.

TABLE 103 R^(Hc) E^(H) G^(H) H CH₂ (2-OMe)Phenyl H CH₂ (2-OH)Phenyl HCH₂—CH₂ Pyridin 3-yl H CH₂—CH₂ Phenyl H CH₂ Pyridin 4-yl H CH₂ Phenyl HCH₂ Pyridin 3-yl H CH₂—CH₂ Cyclohexyl H CH₂—CH₂ Pyridin 4-yl H CH₂Pyridin 2-yl H CH₂—CH₂ Pyridin 2-yl H CH₂ Imidazol 1-yl

TABLE 104 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Imidazol 1-yl H CH₂—CH₂(2-OMe)Phenyl H CH₂—CH₂—CH₂ Phenyl H NH—CH₂ Pyridin 2-yl H CH₂—NH PhenylH CH₂—O Phenyl H CH₂ (6-F) Pyridin 2-yl H CH₂—CH₂ (6-F) Pyridin 2-yl HC(Me)₂ (2-OMe)Phenyl H C(Me)—CH₂ Pyridin 2-yl H CH₂—C(Me)₂ Pyridin 2-ylH CH₂—CH₂ Pyrimidin 2-yl

TABLE 105 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Pyrazine 2-yl H CH₂—CH₂ Pyridazin3-yl H CH₂—C(Me)₂ Pyridin 3-yl 3-F CH(Me) (2-OMe)Phenyl 3-Me CH₂—CH₂Pyridin 3-yl 3-OMe CH₂—CH₂ Phenyl 3,5-F CH₂ Pyridin 4-yl 3-NH₂ CH₂Phenyl 3,6-F CH₂ Pyridin 3-yl 3-OMe CH₂—CH₂ Pyridin 2-yl 3-CN CH₂—CH₂Pyridin 2-yl 3-CF₃ CH₂—CH₂ Pyridin 2-yl

<Representative Compound H-200>

wherein R^(Hc), E^(H), and G^(H) are as described in Tables 106 to 108.

TABLE 106 R^(Hc) E^(H) G^(H) H CH₂ (2-OMe)Phenyl H CH₂ (2-OH)Phenyl HCH₂—CH₂ Pyridin 3-yl H CH₂—CH₂ Phenyl H CH₂ Pyridin 4-yl H CH₂ Phenyl HCH₂ Pyridin 3-yl H CH₂—CH₂ Cyclohexyl H CH₂—CH₂ Pyridin 4-yl H CH₂Pyridin 2-yl H CH₂ Pyridin 2-yl

TABLE 107 R^(Hc) E^(H) G^(H) H CH₂ Imidazole 1-yl H CH₂—CH₂ Imidazole1-yl H CH₂—CH₂ (2-OMe)Phenyl H CH₂ (2-OMe)Phenyl H CH₂—CH₂—CH₂ Phenyl HCH₂ (6-F) Pyridin 2-yl H CH₂—CH₂ (6-F) Pyridin 2-yl H C(Me)₂(2-OMe)Phenyl H C(Me)—CH₂ Pyridin 2-yl H CH₂—C(Me)₂ Pyridin 2-yl HCH₂—CH₂ Pyrimidin 2-yl

TABLE 108 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Pyrazine 2-yl H CH₂—CH₂ Pyridazin3-yl H CH₂—C(Me)₂ Pyridin 3-yl F CH(Me) (2-OMe)Phenyl Me CH₂—CH₂ Pyridin3-yl OMe CH₂—CH₂ Phenyl F CH₂ Pyridin 4-yl Me CH₂ Phenyl OMe CH₂ Pyridin3-yl F CH₂—CH₂ Pyridin 2-yl CN CH₂—CH₂ Pyridin 2-yl F CH₂—CH₂ Pyridin2-yl

<Representative Compound H-300>

wherein R^(Ha), R^(Hc), E^(H), and G^(H) are as described in Tables 109to 111.

TABLE 109 R^(Ha) R^(Hc) E^(H) G^(H) 7-OMe H CH₂ (2-OMe)Phenyl 6-OMe HCH₂ (2-OH)Phenyl 6,7-OMe H CH₂—CH₂ Pyridin 3-yl 7-Me H CH₂—CH₂ Phenyl7-Et H CH₂ Pyridin 4-yl 7-Pr H CH₂ Phenyl 7-iPr H CH₂ Pyridin 3-yl 7-tBuH CH₂—CH₂ Cyclohexyl 7-CN H CH₂—CH₂ Pyridin 4-yl 7-CF₃ H CH₂ Pyridin2-yl 7-OCF₃ H CH₂—CH₂ Pyridin 2-yl

TABLE 110 R^(Ha) R^(Hc) E^(H) G^(H) 7,8-OMe H CH₂ Imidazole 1-yl 6,7-MeH CH₂—CH₂ Imidazole 1-yl 6,7-Cl H CH₂—CH₂ (2-OMe)Phenyl 7,8-Me H CH₂(2-OMe)Phenyl 7,8-Et H CH₂—CH₂—CH₂ Phenyl 7-Cl H CH₂ (6-F) Pyridin 2-yl6-OMe H CH₂—CH₂ (6-F) Pyridin 2-yl 6,7-OMe H C(Me)₂ (2-OMe)Phenyl 7-Me HC(Me)—CH₂ Pyridin 2-yl 7-Et H CH₂—C(Me)₂ Pyridin 2-yl 7-Pr H CH₂—C(Me)₂Pyridin 3-yl

TABLE 111 R^(Ha) R^(Hc) E^(H) G^(H) 7-iPr 3-F CH(Me) (2-OMe)Phenyl 7-tBu3-Me CH₂—CH₂ Pyridin 3-yl 7-CN 3-OMe CH₂—CH₂ Phenyl 7-CF₃ 3,5-F CH₂Pyridin 4-yl 7-OCF₃ 3-NH₂ CH₂ Phenyl 7,8-OMe 3,6-F CH₂ Pyridin 3-yl6,7-Me 3-OMe CH₂—CH₂ Pyridin 2-yl 6,7-Et 3-CN CH₂—CH₂ Pyridin 2-yl7,8-Me 3-CF₃ CH₂—CH₂ Pyridin 2-yl

<Representative Compound H-400>

wherein R^(Hc), E^(H), and G^(H) are as described in Tables 112 to 114.

TABLE 112 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Phenyl H CH₂ (2-OMe)Phenyl H CH₂(2-OH)Phenyl H CH₂—CH₂ Pyridin 2-yl H CH₂—CH₂ Pyridin 3-yl H CH₂—CH₂(2-CF3)Phenyl H CH₂—CH₂ (2-F)Phenyl H CH₂—CH₂ (2-OMe)Phenyl H CH₂Pyridin 4-yl H CH₂ Phenyl H CH₂ Pyridin 3-yl H CH₂ Cyclohexyl H CH₂Pyridin 4-yl

TABLE 113 R^(Hc) E^(H) G^(H) H CH₂ Pyridin 2-yl H CH₂—CH₂ Pyridin 2-yl HCH₂—CH₂ (4-SO₂Me)Phenyl H CH₂—CH₂ (4-F)Phenyl H CH₂—CH₂ (4-CF₃)Phenyl HCH₂—CH₂ (4-CONH₂)Phenyl H CH₂—CH₂—CH₂ Phenyl H CH₂ (6-F) Pyridin 2-yl HCH₂—CH₂ (6-F) Pyridin 2-yl H C(Me)₂ (2-OMe)Phenyl H C(Me)—CH₂ Pyridin2-yl H CH₂—C(Me)₂ Pyridin 2-yl H CH₂—CH₂ Pyrimidin 2-yl

TABLE 114 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Pyrazin 2-yl H CH₂—CH₂ Pyridazin3-yl H CH₂—C(Me)₂ Pyridin 3-yl 3-F CH(Me) (2-OMe)Phenyl 3-Me CH₂—CH₂Pyridin 3-yl 3-OMe CH₂—CH₂ Phenyl 3,5-F CH₂ Pyridin 4-yl 3-NH₂ CH₂Phenyl 3,6-F CH₂ Pyridin 3-yl 3-OMe CH₂—CH₂ Pyridin 2-yl 3-CN CH₂—CH₂Pyridin 2-yl 3-CF₃ CH₂—CH₂ Pyridin 2-yl

<Representative Compound H-500>

wherein R^(Hc), E^(H), and G^(H) are as described in Tables 115 to 117.

TABLE 115 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Phenyl H CH₂ (2-OMe)Phenyl H CH₂(2-OH)Phenyl H CH₂—CH₂ Pyridin 3-yl H CH₂—CH₂ Phenyl H CH₂ Pyridin 4-ylH CH₂ Phenyl H CH₂ Pyridin 3-yl H CH₂—CH₂ Cyclohexyl H CH₂—CH₂ Pyridin4-yl H CH₂ Pyridin 2-yl H CH₂—CH₂ Pyridin 2-yl

TABLE 116 R^(Hc) E^(H) G^(H) H CH₂ Imidazole 1-yl H CH₂—CH₂ Imidazole1-yl H CH₂—CH₂ (2-OMe)Phenyl H CH₂ (2-OMe)Phenyl H CH₂—CH₂—CH₂ Phenyl HCH₂ (6-F) Pyridin 2-yl H CH₂—CH₂ (6-F) Pyridin 2-yl H C(Me)₂(2-OMe)Phenyl H C(Me)—CH₂ Pyridin 2-yl H CH₂—C(Me)₂ Pyridin 2-yl HCH₂—CH₂ Pyrimidin 2-yl H CH₂—CH₂ Pyrazin 2-yl

TABLE 117 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Pyridazin 3-yl H CH₂—C(Me)₂Pyridin 3-yl 3-F CH(Me) (2-OMe)Phenyl 3-Me CH₂—CH₂ Pyridin 3-yl 3-OMeCH₂—CH₂ Phenyl 3,5-F CH₂ Pyridin 4-yl 3-NH₂ CH₂ Phenyl 3,6-F CH₂ Pyridin3-yl 3-OMe CH₂—CH₂ Pyridin 2-yl 3-CN CH₂—CH₂ Pyridin 2-yl 3-CF₃ CH₂—CH₂Pyridin 2-yl

<Representative Compound H-600>

wherein R^(Hc), E^(H), and G^(H) are as described in Tables 118 to 120.

TABLE 118 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Pyridin 2-yl H CH₂ (2-OMe)PhenylH CH₂ (2-OH)Phenyl H CH₂—CH₂ Pyridin 3-yl H CH₂—CH₂ Phenyl H CH₂ Pyridin4-yl H CH₂ Phenyl H CH₂ Pyridin 3-yl H CH₂—CH₂ Cyclohexyl H CH₂—CH₂Pyridin 4-yl H CH₂ Pyridin 2-yl H CH₂ Imidazol 1-yl

TABLE 119 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Imidazol 1-yl H CH₂—CH₂(2-OMe)Phenyl H CH₂ (2-OMe)Phenyl H CH₂—CH₂—CH₂ Phenyl H CH₂ (6-F)Pyridin 2-yl H CH₂—CH₂ (6-F) Pyridin 2-yl H C(Me)₂ (2-OMe)Phenyl HC(Me)—CH₂ Pyridin 2-yl H CH₂—C(Me)₂ Pyridin 2-yl H CH₂—C(Me)₂ Pyridin3-yl 3-F CH(Me) (2-OMe)Phenyl 3-Me CH₂—CH₂ Pyridin 3-yl

TABLE 120 R^(Hc) E^(H) G^(H) 3-OMe CH₂—CH₂ Phenyl 3,5-F CH₂ Pyridin 4-yl3-NH₂ CH₂ Phenyl 3,6-F CH₂ Pyridin 3-yl 3-OMe CH₂—CH₂ Pyridin 2-yl 3-CNCH₂—CH₂ Pyridin 2-yl 3-CF₃ CH₂—CH₂ Pyridin 2-yl

<Representative Compound H-700>

wherein R^(Hc), E^(H), and G^(H) are as described in Tables 121 to 123.

TABLE 121 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Phenyl H CH₂ (2-OMe)Phenyl H CH₂(2-OH)Phenyl H CH₂—CH₂ Pyridin 3-yl H CH₂—CH₂ Phenyl H CH₂ Pyridin 4-ylH CH₂ Phenyl H CH₂ Pyridin 3-yl H CH₂ Cyclohexyl H CH₂—CH₂ Pyridin 4-ylH CH₂ Pyridin 2-yl H CH₂—CH₂ Pyridin 2-yl

TABLE 122 R^(Hc) E^(H) G^(H) H CH₂ Imidazole 1-yl H CH₂—CH₂ Imidazole1-yl H CH₂—CH₂ (2-OMe)Phenyl H CH₂ (2-OMe)Phenyl H CH₂—CH₂—CH₂ Phenyl HCH₂ (6-F) Pyridin 2-yl H CH₂—CH₂ (6-F) Pyridin 2-yl H C(Me)₂(2-OMe)Phenyl H C(Me)—CH₂ Pyridin 2-yl H CH₂—C(Me)₂ Pyridin 2-yl HCH₂—CH₂ Pyrimidin 2-yl H CH₂—CH₂ Pyrazin 2-yl

TABLE 123 R^(Hc) E^(H) G^(H) H CH₂—CH₂ Pyridazin 3-yl H CH₂—C(Me)₂Pyridin 3-yl 3-F CH(Me) (2-OMe)Phenyl 3-Me CH₂—CH₂ Pyridin 3-yl 3-OMeCH₂—CH₂ Phenyl 3,5-F CH2 Pyridin 4-yl 3-NH₂ CH2 Phenyl 3,6-F CH2 Pyridin3-yl 3-OMe CH₂—CH₂ Pyridin 2-yl 3-CN CH₂—CH₂ Pyridin 2-yl 3-CF₃ CH₂—CH₂Pyridin 2-yl

<Representative Compound H-800>

wherein the tetrazole ring substitution position, E^(H)-G^(H), n^(H),and the salt are as described in Table 124.

TABLE 124 Tetrazole ring substitution position E^(H)-G^(H) n^(H) Salt 3CH₂CH₂(2-Py) 0 4 CH₂CH₂(6-methylpyridin-2-yl) 1 4 CH₂CH₂(3-CN)Ph 1 4CH₂CH₂(3-CONH₂)Ph 1 4 CH₂CH₂(2-methoxypyridin-3-yl) 1 4 CH2(2-NMe₂)Ph 1MsOH 4 CH₂C(Me)₂(2-Py) 1 HCl 4 CH₂CH₂(3-methoxypyridin-2-yl) 1 HCl 3CH₂CH₂CH₂(6-methylpyridin-2-yl) 1 3 CH₂CH₂CH₂(3-CN)Ph 1 3CH₂CH₂CH₂(3-CONH₂)Ph 1 3 CH₂CH₂CH₂(2-methoxypyridin-3-yl) 1 3CH₂CH₂(2-NMe₂)Ph 1 3 CH₂CH₂C(Me)₂(2-Py) 0 3CH₂CH₂CH₂(3-methoxypyridin-2-yl) 0

<Representative Compound H-900>

Naphthalene Form

Indane Form

wherein E^(H)-G^(H), R^(H), and the salt are as described in Tables 125and 126.

TABLE 125 Naphthalene form or Indane form E^(H)-G^(H) R^(H) SaltNaphthalene form CH₂CH₂(3-F)Ph H HCl Naphthalene form CH₂CH₂(2-OMe)Ph HHCl Naphthalene form CH₂CH₂(4-F)Ph H HCl Naphthalene form CH₂CH₂(2-F)PhH HCl Naphthalene form CH₂CH₂(4-CF3)Ph H HCl Naphthalene formCH₂CH₂(2,6-Me)Ph H HCl Naphthalene form CH₂CH₂(3-CF3)Ph H HClNaphthalene form CH₂CH₂(3-OMe)Ph H HCl Naphthalene form CH₂CH₂(3-OH)Ph HHCl Naphthalene form CH₂CH₂(4-CN)Ph H Naphthalene form CH₂CH₂(4-CONH₂)PhH Naphthalene form CH₂CH₂(2-CN)Ph H Naphthalene form CH₂CH₂(2-CONH₂)Ph HNaphthalene form CH₂CH₂(3-CN)Ph H Naphthalene form CH₂CH₂(3-CONH₂)Ph HNaphthalene form CH₂CH₂(3-CONH₂)Ph H HCl Naphthalene formCH₂CH₂(4-SO₂Me)Ph H HCl Naphthalene form CH₂CH₂(3-OMe, 2-F)Ph H HCl

TABLE 126 Naphthalene form or Indane form E^(H)-G^(H) R^(H) Salt Indaneform CH₂CH₂(3-OMe, 2-F)Ph H HCl Naphthalene form CH₂CH₂(3-thienyl) H HClNaphthalene form CH₂CH₂(2-furanyl) H HCl Indane form CH₂CH₂(2-F)Ph HNaphthalene form CH₂CH₂(2-Pyridyl) H 2HCl Indane form CH₂CH₂(3-F)Ph HHCl Naphthalene form CH₂CH₂(2-OMe, 3-F)Ph H HCl Naphthalene formCH₂CH₂(3-F)Ph F Naphthalene form CH₂CH₂(2-OMe)Ph OH Naphthalene formCH₂CH₂(4-F)Ph H Naphthalene form CH₂CH₂(2-F)Ph F Naphthalene formCH₂CH₂(4-CF₃)Ph OH Naphthalene form CH₂CH₂(2,6-Me)Ph H Naphthalene formCH₂CH₂(3-CF₃)Ph F Naphthalene form CH₂CH₂(3-OMe)Ph OH Naphthalene formCH₂CH₂(3-OH)Ph H Naphthalene form CH₂CH₂(4-CN)Ph F Indane formCH₂CH₂(2,6-Me)Ph H Indane form CH₂CH₂(3-CF3)Ph F Indane formCH₂CH₂(3-OMe)Ph OH Indane form CH₂CH₂(3-OH)Ph H Indane formCH₂CH₂(4-CN)Ph F

<Representative Compound H-1000>

wherein E^(H)-G^(H), R^(H), and the salt are as described in Table 127.

TABLE 127 E^(H)-G^(H) R^(H) bond-Ph H bond-(2-OMe)Ph H CH₂OPh HNH-(2-OMe)Ph H NH—Ph H CH₂SPh F CH₂NHPh OH bond-(2-F)Ph F bond-(2CF₃)PhOH bond-(2Cl)Ph F bond-(2-Me)Ph OH bond-(2,6-Me)Ph F bond-(2,6-F)Ph OHbond-(2-OH)Ph F CH₂O(2-F)Ph OH NH-(2,6-Me)Ph F NH-(2CF₃)Ph OHbond-(3-F)Ph F

<Representative Compound H-1100>

wherein E^(H)-G^(H), R^(H), and the salt are as described in Table 128.

TABLE 128 E^(H)-G^(H) R^(H) Salt CH₂CH₂Ph H HCl CH₂(4-Cl)Ph H HClCH₂(2-OMe)Ph H CH₂CH₂(3-OMe)Ph H CH₂CH₂(3-OMe)Ph H HCl CH₂CH₂(3-OH)Ph HCH₂(2,4,6-Me)Ph H HCl CH₂(2-CF₃)Ph H HCl CH₂(2-CN)Ph H CH₂(2-CONH₂)Ph HCH₂(2-NH₂)Ph H CH₂CH₂Ph OMe CH₂CH₂Ph OH CH₂(3-CN)Ph H CH₂(3-CONH₂)Ph HCH₂CH₂(3-OMe)Ph F CH₂CH₂(3-OH)Ph F CH₂CH₂(3-F)Ph H CH₂CH₂(2-F)Ph FCH₂CH₂(2-F)Ph H

<Representative Compound H-1200>

wherein E^(H)-G^(H), R^(H), and the salt are as described in Table 129.

TABLE 129 E^(H)-G^(H) R^(H) Salt bond-Ph H HCl CH₂CH₂Ph H HClCH₂CH₂(2-F)Ph H CH₂CH₂(3-F)Ph F CH₂CH₂(2-OMe)Ph F CH₂CH₂(3-OMe)Ph FCH₂CH₂(2-OH)Ph F CH₂CH₂(3-OH)Ph F

<Representative Compound H-1300>

wherein E^(H)-G^(H), R^(H), and the salt are as described in Table 130.

TABLE 130 E^(H)-G^(H) R^(H) Salt CH₂CH₂Ph H HCl CH₂CH₂(2-F)Ph HCH₂CH₂(3-F)Ph F CH₂CH₂(2-OMe)Ph F CH₂CH₂(3-OMe)Ph F CH₂CH₂(2-OH)Ph FCH₂CH₂(3-OH)Ph F

WO 2010/093061 discloses the compounds represented by general formulas(AI) and (AII), WO 2012/008478 discloses the compounds represented bygeneral formulas (BI) to (BIII), WO 2012/014910 discloses the compoundsrepresented by general formulas (CI) and (CII), and WO 2012/017876discloses the compounds represented by general formulas (DI) and (DII).Thus, these compounds are readily available by consulting these WOpamphlets. All the disclosures in their WO pamphlets are hereinincorporated by reference in the entirety.

Although part of general formula (AI) (e.g., compounds A20 and A21 ofExamples) is not disclosed in WO 2010/093061, the correspondingcompounds are readily available by consulting the synthesis scheme(process 3) described in WO 2008/023847 and WO 2010/093061 orparagraphs[0054] to[0060](synthesis process 2) in WO 2012/017876. Allthe disclosures in their WO pamphlets are herein incorporated byreference in the entirety.

Note that the compounds represented by general formula (EI) fall underpart of the compounds represented by general formulas (AI) to (DII).Thus, these compounds are readily available by consulting WO2008/023847, WO 2010/093061, WO 2012/008478, WO 2012/014910, and WO2012/017876.

In addition, WO 2013/105608 discloses the compounds represented bygeneral formulas (FI) and (FII) and WO 2015/005467 discloses thecompounds represented by general formula (GI). Thus, these compounds arereadily available by consulting these WO pamphlets. All the disclosuresin their WO pamphlets are herein incorporated by reference in theentirety.

Further, WO 2015/005468 discloses the compounds represented by generalformulas (HI) and (HII). Thus, these compounds are readily available byconsulting the WO pamphlet. All the disclosures in their WO pamphletsare herein incorporated by reference in the entirety.

Meanwhile, the above WO 2010/093061, WO 2012/008478, WO 2012/014910, WO2012/017876, WO 2013/105608, WO 2015/005467, and WO 2015/005468 describethat the compounds represented by general formulas (AI) to (HII) exertP2X4 receptor antagonistic effects.

Note that the following shows specific examples of preferable compoundsand pharmaceutically acceptable salts thereof included in the compoundsrepresented by general formulas (AI) to (HII). However, a compound orpharmaceutically acceptable salt thereof that can be utilized as anactive ingredient in a medicament of the present invention is notlimited to them.

(Compound A1)5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A2)5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound A3)5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionepotassium salt;

(Compound A4)5-[4-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A5)5-[4-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound A6)1-methyl-5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A7)1,3-dimethyl-5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A8)5-[2-chloro-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A9)5-[2-chloro-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound A10)5-[2-methyl-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A11)5-[2-methyl-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound A12)5-[2-bromo-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A13)5-[3-(2-methyl-2H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A14)5-[3-(1-methyl-1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A15)5-[3-(5-oxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A16)5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A17)5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound A18)5-[3-(oxazol-2-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;and

(Compound A19)5-[3-(1H-pyrazol-4-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound A20)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-one;

(Compound A21)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-onesodium salt;

(Compound A22)5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;and

(Compound A23)5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt.

(Compound B1)5-(3-cyanophenyl)-8,9,10,11-tetrahydronaphtho[2,1-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound B2)5-[3-(1H-tetrazol-5-yl)phenyl]-8,9,10,11-tetrahydronaphtho[2,1-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound B3)5-(3-hydroxyphenyl)-8,9,10,11-tetrahydronaphtho[2,1-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound B4)5-(3-cyanophenyl)-5,8,9,10-tetrahydroindeno[5,4-b][1,4]diazepin-2,4(1H,3H)-dione;

(Compound B5)5-[3-(1H-tetrazol-5-yl)phenyl)-5,8,9,10-tetrahydroindeno[5,4-b][1,4]diazepin-2,4(1H,3H)-dionesodium salt;

(Compound B6)5-[3-(2-methyl-2H-tetrazol-5-yl)phenyl)-5,8,9,10-tetrahydroindeno[5,4-b][1,4]diazepin-2,4(1H,3H)-dione;

(Compound B7)5-[3-(1-methyl-1H-tetrazol-5-yl)phenyl)-5,8,9,10-tetrahydroindeno[5,4-b][1,4]diazepin-2,4(1H,3H)-dione;

(Compound B8)5-(3-tert-butoxycarbonylaminophenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B9)5-(3-aminophenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dionehydrochloride;

(Compound B10)5-[3-(2-methyl-2H-tetrazol-5-yl)phenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B11)5-[3-(1-methyl-1H-tetrazol-5-yl)phenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B12)5-(4-aminophenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B13)5-(4-methylaminophenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dionehydrochloride;

(Compound B14)5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B15)5-(4-methoxyphenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B16)5-(4-hydroxyphenyl)-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B17)5-[4-(isopropylcarbonylamino)phenyl]-1,5,8,9,10,11-hexahydronaphtho[1,2-b][1,4]diazepin-2,4-dione;

(Compound B18)5-(3-carbamoylphenyl)-1,5,8,10-tetrahydro-1H-indeno[6,7-b][1,4]diazepin-2,4-dione;

(Compound B19)1-acetyl-5-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)phenyl]-1,5,8,10-tetrahydro-1H-indeno[6,7-b][1,4]diazepin-2,4-dione;

(Compound B20)5-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)phenyl]-1,5,8,10-tetrahydro-1H-indeno[6,7-b][1,4]diazepin-2,4-dione;and

(Compound B21)5-[3-(5-phenyl-[1,3,4]oxadiazol-2-yl)phenyl]-1,5,8,10-tetrahydro-1H-indeno[6,7-b][1,4]diazepin-2,4-dione.

(Compound C1) 4-(3-cyanophenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound C2)4-[3-(1H-tetrazol-5-yl)phenyl]-1,4-dihydrobenzo[f]quinoxalin-2,3-dionesodium salt;

(Compound C3)4-(3-methoxyphenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound C4)4-(3-hydroxyphenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dione sodium salt;

(Compound C5)5-(3-methoxyphenyl)-1,4,7,8,9,10-hexahydrobenzo[f]quinoxalin-2,3-dione;

(Compound C6)5-(3-hydroxyphenyl)-1,4,7,8,9,10-hexahydrobenzo[f]quinoxalin-2,3-dione;

(Compound C7)4-(3-aminophenyl)-1,4,7,8,9,10-hexahydrobenzo[f]quinoxalin-2,3-dionehydrochloride;

(Compound C8)4-(1H-indol-4-yl)-1,4,7,8,9,10-hexahydrobenzo[f]quinoxalin-2,3-dione;

(Compound C9)N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydrobenzo[f]quinoxalin-4(1H)-yl)phenyl]-2-nitrobenzenesulfonamide;

(Compound C10)4-(3-methylaminophenyl)-1,4,7,8,9,10-hexahydrobenzo[f]quinoxalin-2,3-dionehydrochloride;

(Compound C11)1-methyl-4-(3-methylaminophenyl)-1,4,7,8,9,10-hexahydrobenzo[f]quinoxalin-2,3-dionehydrochloride;

(Compound C12)4-(3-fluorophenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound C13) 4-(3-aminophenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dionehydrochloride;

(Compound C14)4-[3-[(2-iodophenylacetyl)amino]phenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound C15)4-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)phenyl]-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound C16)4-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)phenyl]-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound C17)4-(4-hydroxyphenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dione sodium salt;

(Compound C18) 4-(4-aminophenyl)-1,4-dihydrobenzo[f]quinoxalin-2,3-dionehydrochloride;

(Compound C19)N-[4-(2,3-dioxo-2,3-dihydrobenzo[f]quinoxalin-4(1H)-yl)phenyl]-2-nitrobenzenesulfonamide;

(Compound C20)4-[4-(5-methyl-[1,3,4]oxadiazol-2-yl)phenyl]-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound C21)4-[3-[2-(trifluoromethyl)benzoyl]aminophenyl]-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-2,3-dione;

(Compound C22)N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-4-yl)phenyl]benzenesulfonamide;

(Compound C23)3-bromo-N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-4-yl)phenyl]benzenesulfonamide;

(Compound C24)N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-4-yl)phenyl]-1-naphthalenesulfonamide;

(Compound C25)N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-4-yl)phenyl]-2-naphthalenesulfonamide;

(Compound C26)N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-4-yl)phenyl]-2-thiophenesulfonamide;

(Compound C27)N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-4-yl)phenyl]-3-pyridinesulfonamide hydrochloride;

(Compound C28)N-[3-(2,3-dioxo-2,3,7,8,9,10-hexahydro-1H-benzo[f]quinoxalin-4-yl)phenyl]-8-quinolinesulfonamide hydrochloride; and

(Compound C29)4-[3-(1H-tetrazol-1-yl)phenyl]-2,3,7,8,9,10-tetrahydro-1H-benzo[f]quinoxalin-2,3-dione.

(Compound D1) 4-(3-cyanophenyl)-1H-benzo[h]quinazolin-2-one;

(Compound D2) 4-[3-(1H-tetrazol-5-yl)phenyl]-1H-benzo[h]quinazolin-2-onesodium salt;

(Compound D3) 4-(3-methoxyphenyl)-1H-benzo[h]quinazolin-2-one;

(Compound D4) 4-(3-hydroxyphenyl)-1H-benzo[h]quinazolin-2-one sodiumsalt;

(Compound D5) 4-(4-methoxyphenyl)-1H-benzo[h]quinazolin-2-one;

(Compound D6) 4-(4-hydroxyphenyl)-1H-benzo[h]quinazolin-2-one sodiumsalt;

(Compound D7) 4-(3-aminophenyl)-1H-benzo[h]quinazolin-2-onehydrochloride; and

(Compound D8)N-[3-(2-oxo-1,2-dihydrobenzo[h]quinazolin-4-yl)phenyl]benzenesulfonamide.

(Compound E1)5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound E2)5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound E3)5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionepotassium salt;

(Compound E4)5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound E5)5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound E6)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-one;

(Compound E7)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-onesodium salt;

(Compound E8)5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound E9)5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound E10)5-[3-(1H-tetrazol-5-yl)phenyl]-8,9,10,11-tetrahydronaphtho[2,1-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound E11)5-[3-(1H-tetrazol-5-yl)phenyl]-8,9,10,11-tetrahydronaphtho[2,1-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;

(Compound E12)4-[3-(1H-tetrazol-5-yl)phenyl]-1,4-dihydrobenzo[f]quinoxalin-2,3-dione;

(Compound E13)4-[3-(1H-tetrazol-5-yl)phenyl]-1,4-dihydrobenzo[f]quinoxalin-2,3-dionesodium salt;

(Compound E14)4-[3-(1H-tetrazol-5-yl)phenyl]-1H-benzo[h]quinazolin-2-one; and

(Compound E15)4-[3-(1H-tetrazol-5-yl)phenyl]-1H-benzo[h]quinazolin-2-one sodium salt.

(Compound F1)5-(4-benzoylaminophenyl)-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F2)5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F3)5-[4-(3-bromobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F4)5-[4-[4-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F5)5-[4-(2-methylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F6)5-[4-(2,6-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F7)5-[4-(2,6-dichlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F8)5-[4-(3-chlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F9)5[4-(2-phenylacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F10)1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylthiourea;

(Compound F11)5-[4-(2,3-dimethoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F12)5-[4-(2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F13)5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F14)5-[4-(2,3-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F15)5-[4-(2,5-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F16)5-[4-(5-bromo-2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F17)5-[4-(2,4-dichlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F18)5-[4-(2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F19)5-[4-(2,3-dihydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F20)1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylurea;

(Compound F21)5-[4-[(2,6-dichlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F22)5-[4-[(2-methoxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F23)5-[4-[(2-hydroxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F24)1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]thiourea;

(Compound F25)5-[4-[3-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F26)5-[4-[2-[2-(trifluoromethyl)phenyl]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F27)1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]urea;

(Compound F28)5-[4-[(2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F29)5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F30)5-[4-(3-phenylpropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F31)5-[4-[(1H-indole-3-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F32)5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F33)5-[4-[(2-methyl-2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F34)5-[4-(2-phenoxyacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F35)5-[4-[2-(2-chloro-4-methoxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F36)5-[4-[(1-methyl-1H-imidazole-2-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F37)5-[4-[2-(2,4-dichlorophenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F38)5-[4-[2-(2-chloro-4-hydroxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F39)5-[4-(3-phenylpropenylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F40)5-[4-[(3-pyridylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound F41)5-[4-(1H-benzimidazole-2-carbonylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F42)1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-methoxy-1H-1,5-benzodiazepin-2,4(3H,5H)-dione;

(Compound F43)5-[4-[(benzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F44)5-[4-[(2-chlorobenzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F45)1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-hydroxy-1H-1,5-benzodiazepin-2,4(3H,5H)-dione;

(Compound F46)5-[4-(2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F47)5-[4-(2-bromobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F48)5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F49)5-[4-(2,3-dimethylbenzoylamino)-3-fluorophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F50)5-[4-[2-(2-methylphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F51)5-[4-[(quinoxalin-2yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F52)5-[4-[(5-methylthiophen-2yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F53)5-[3-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F54)5-[4-[(2,4,6-trimethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F55)5-[4-(cyclohexylcarbonylamino)phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F56)1-[4-(2,3-dimethylbenzoyl)aminophenyl]-6-methyl-1H-1,5-benzodiazepin-2,4(3H,5H)-dione;

(Compound F57)5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F58)5-[4-[(6-methylpyridin-2-yl)carbonylamino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F59)5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F60)1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-(2-methylphenyl)thiourea;

(Compound F61)5-[4-(2-methoxy-3-methylbenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F62)5-[4-(2,3-dichlorobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F63)5-[4-(2,3-dimethylbenzoylamino)-3-hydroxyphenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F64)5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;

(Compound F65)5-[4-[(4-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F66)5-[4-[2-(2,4-dichlorophenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F67)5-[4-[2-(2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F68)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)butyl]-2-chloro-3-methoxybenzamide;

(Compound F69)5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;

(Compound F70)5-[4-(2-acetylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F71)5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F72)5-[2-(2-iodobenzoyl)aminoethyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F73)5-[3-[(2-iodobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F74)6,7-dimethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepin-2,4(3H,5H)-dione;

(Compound F75)5-[4-[(1-methylpiperidin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound F76)5[4-[(benzofuran-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F77)5-[4-[(1-methyl-1H-indol-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F78)5-[4-(2-propenylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F79)5-[4-(2-propylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F80)5-[3-fluoro-4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F81)5-[4-(2-hydroxy-3-methylbenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F82)5-[4-[(2-isopropoxybenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F83)5-[4-[(3-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F84)5-[4-(2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F85)5-[4-[2-(4-chloro-2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F86)5-[4-[(4-fluoro-2-trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F87)5-[4-(4-fluoro-2-methoxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F88)5-[4-(4-fluoro-2-hydroxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F89)5-[3-[(2-iodophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F90)5-[4-(2-methyl-2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F91)5-[4-(2-tert-butylbenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;

(Compound F92)5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F93)5-[4-(4-iodo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F94)5-[4-(6-fluoro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F95)5-[4-(2-hydroxy-4-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F96)5-[4-(6-fluoro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F97)5-[4-(2-fluorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F98)5-[4-[(2-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F99)5-[4-(2-methoxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F100)5-[4-(2-hydroxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F101)5-[4-[3-(2-methylphenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F102)5-(4-phenylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F103)5-(4-benzylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F104)5-[4-[3-(2-methylphenyl)propenoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F105)5-[4-[3-(2-chlorophenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F106)5-[4-(2-iodobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F107)5-[4-[(1-methyl-1H-pyrrol-2-ylacetyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F108)5-[4-(2-chlorobenzyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F109)5-[4-[3-(2-chlorophenyl)propenoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F110)5-[4-(2-chlorophenyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F111)5-[4-(6-bromo-2,3-methylenedioxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F112)5-[4-(6-bromo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F113)5-[4-[(2-tert-butylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F114)5-[2-(2-iodobenzoyl)aminopyridin-5-yl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F115)5-[4-(6-bromo-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F116)5-[4-(6-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F117)5-[4-(2-iodobenzoylamino)phenyl]-1H-[1,4]diazepino[2,3-h]quinoline-2,4(3H,5H)-dione;

(Compound F118)5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F119)5-[4-(2-hydroxy-6-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F120)5-[4-[2-methoxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F121)5-[4-[2-hydroxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F122)5-[4-[(2-isopropenylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F123)5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F124)5-[4-[2-chloro-5-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F125)5-[4-[2-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F126)5-[4-[3-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F127)5-[4-[2-ethyl-6-methoxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F128) 5-[4-(3-methanesulfonylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F129)6-ethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepin-2,4(3H,5H)-dione;

(Compound F130)5-[4-[2-ethyl-6-hydroxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F131)5-[4-(3-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F132)5-[4-(2-chloro-5-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F133)5-[4-(2-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F134)5-[4-[[2-(4-morpholinyl)acetyl]amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound F135)5-[4-(2-chloro-6-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;

(Compound F136)5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F137)5-[4-(2-chloro-6-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;

(Compound F138)5-[4-(3-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F139)5-[4-[(3-methylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F140)5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F141)5-[4-(3-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F142)5-[4-[[(3-hydroxypyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F143)5-[4-[(3-vinylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F144)5-[4-[(3-ethylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F145)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitrobenzenesulfonamide;

(Compound F146)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide;

(Compound F147)3-bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide;

(Compound F148)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-methoxybenzenesulfonamide;

(Compound F149)N-[3-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]benzenesulfonamide;

(Compound F150)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitrobenzenesulfonamide;

(Compound F151)N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitrobenzenesulfonamide;

(Compound F152)N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

(Compound F153)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

(Compound F154)4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)-N-phenylbenzenesulfonamide;

(Compound F155)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepin-5-yl)phenyl]-2-naphthalenesulfonamide;

(Compound F156)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepin-5-yl)phenyl]-1-naphthalenesulfonamide;

(Compound F157)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]cyclohexanesulfonamide;

(Compound F158)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-3-pyridinesulfonamide hydrochloride;

(Compound F159)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-4-isopropylbenzenesulfonamide;

(Compound F160)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenylmethanesulfonamide;

(Compound F161)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-3-pyridinesulfonamide;

(Compound F162)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-naphthalenesulfonamide;

(Compound F163)4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho-[1,2-b][1,4]diazepin-5-yl)phenyl3-bromobenzene-sulfonate;

(Compound F164)N-benzyl-N-[4-(1-benzyl-2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-nitrobenzenesulfonamide;

(Compound F165)N-benzyl-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-nitrobenzenesulfonamide;

(Compound F166)3-bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-N-methylbenzenesulfonamide;

(Compound F167)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

(Compound F168)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-(2-hydroxyethyl)-2-nitrobenzenesulfonamide;

(Compound F169)N-[4-(7-chloro-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide;

(Compound F170)N-[4-(7-bromo-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide;

(Compound F171)N-[4-[(2,4-dioxo-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)]phenyl]benzenesulfonamide;

(Compound F172)N-[4-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide;

(Compound F173)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F174)1-(3-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F175)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-trifluoromethylbenzene sulfonamide;

(Compound F176)N-[4-(7-bromo-6-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide;

(Compound F177)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F178)3-bromo-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide;

(Compound F179)N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-methoxybenzenesulfonamide;

(Compound F180)1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F181)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide;

(Compound F182)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-nitrophenyl)methanesulfonamide;

(Compound F183)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-2-phenylethanesulfonamide;

(Compound F184)1-(2,3-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F185)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-methoxy-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide;

(Compound F186)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-hydroxy-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide;

(Compound F187)1-(4-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F188)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)benzyl]methanesulfonamide;

(Compound F189)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)-2-methoxyphenyl]methanesulfonamide;

(Compound F190)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)-2-hydroxyphenyl]methanesulfonamide;

(Compound F191)1-(2,6-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F192)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-6-methyl-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide;

(Compound F193)1-(2-chlorophenyl)-N-[4-(2,4-dioxy-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)propyl]methanesulfonamide;

(Compound F194)1-(2-chlorophenyl)-N-[2-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)ethyl]methanesulfonamide;

(Compound F195)N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-iodophenyl)methanesulfonamide;

(Compound F196)1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-N-methylmethanesulfonamide;

(Compound F197)1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

(Compound F198)1-[2-(trifluoromethyl)phenyl]-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

(Compound F199)1-(2-ethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

(Compound F200)1-(2,3-dimethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

(Compound F201)2-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylethanesulfonamide;

(Compound F202)1-(2-nitrophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

(Compound F203)1-(2-aminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

(Compound F204)1-(2-dimethylaminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

(Compound F205)5-[4-[(pyridin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound F206)5-[4-[2-[(pyridin-3-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound F207)5-[4-[(pyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound F208)5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound F209)5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F210)5-[4-[2-[(pyridin-2-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F211)5-[4-[[4-(trifluoromethyl)pyridin-3-yl]carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound F212)5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-[1,4]diazepino[2,3-f]isoquinolin-2,4(3H,5H)-dione;

(Compound F213)5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-8,9,10,11-tetrahydro-1H-[1,4]diazepino[2,3-f]isoquinolin-2,4(3H,5H)-dione;and

(Compound F214)5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione.

(Compound G1)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-3-(pyridin-2-yl)propionamide;

(Compound G2)2-ethyl-3-hydroxy-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]benzamide;

(Compound G3)2-ethyl-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]nicotinamidedihydrochloride;

(Compound G4)2-ethyl-6-hydroxy-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]benzamide;

(Compound G5)3-ethyl-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]picolinamidehydrochloride;

(Compound G6)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-2-(pyridin-2-yloxy)acetamidehydrochloride;

(Compound G7)2-(2-methoxyphenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]acetamide;

(Compound G8)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)-phenyl]-3-(pyridin-3-yl)propionamidedihydrochloride;

(Compound G9)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]-3-phenylpropanamide;

(Compound G10)N-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)-phenyl]-3-(pyridin-3-yl)propionamidehydrochloride;

(Compound G11)N-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)-phenyl]-3-(pyridin-4-yl)propionamidehydrochloride;

(Compound G12)2-tert-butyl-N-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)2-fluorophenyl]benzamide;

(Compound G13)N-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)-phenyl]-3-(pyridin-2-yl)propionamidehydrochloride;

(Compound G14)2-(dimethylamino)-N-[4-(2,4-dioxo-2,3-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]nicotinamide hydrochloride;

(Compound G15)2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamide;

(Compound G16)2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamidedihydrochloride;

(Compound G17)

2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedimethanesulfonate;

(Compound G18)N-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]-diazepin-5(2H)-yl)phenyl]-2-(morpholin-4-yl)-nicotinamide hydrochloride;

(Compound G19)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-2-(1H-pyrrol-1-yl)nicotinamidedihydrochloride;

(Compound G20)2-(morpholin-4-yl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]nicotinamidedihydrochloride;

(Compound G21)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-2-(pyrrolidin-1-yl)nicotinamidedihydrochloride;

(Compound G22)4-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamidedihydrochloride;

(Compound G23)2-isopropyl-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedihydrochloride; and

(Compound G24)2-(isopropylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamidedihydrochloride.

(Compound H1)5-[4-[5-(2-methoxybenzyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H2)5-[4-[5-(2-hydroxybenzyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H3)5-[4-[5-[2-(pyridin-3-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H4)5-[4-(5-phenethyl-1H-tetrazol-1-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H5)5-[4-[5-(pyridin-4-ylmethyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H6)5-[4-(5-benzyl-1H-tetrazol-1-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H7)5-[4-[5-(pyridin-3-ylmethyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H8)7-methoxy-1-[4-[5-(2-methoxybenzyl)-1H-tetrazol-1-yl]phenyl]-1H-benzo[b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H9)5-[6-[5-(2-methoxybenzyl)-1H-tetrazol-1-yl]pyridin-3-yl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H10)5-[4-[5-(2-cyclohexylethyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H11)5-[6-[5-(2-hydroxybenzyl)-1H-tetrazol-1-yl]pyridin-3-yl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H12)5-[4-[5-[2-(pyridin-4-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H13)5-[4-[5-(pyridin-2-ylmethyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H14)5-[4-[5-[2-(pyridin-2-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H15)5-[4-[5-[(1H-imidazol-1-yl)methyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H16)5-[4-[5-[2-(1H-imidazol-1-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H17)5-[4-[5-[2-(pyridin-2-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-one dihydrochloride;

(Compound H18)5-[4-[5-(2-methoxyphenethyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H19)5-[4-[5-(2-methoxybenzyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-one;

(Compound H20)5-[4-[5-(3-phenylpropyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H21)5-[4-(2-phenethyl-1H-imidazol-1-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H22)5-[4-(1-phenethyl-1H-imidazol-2-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H23)5-[4-[1-(4-chlorobenzyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H24)5-[4-[1-(2-methoxybenzyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H25)5-[4-[1-(3-methoxyphenethyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H26)5-[4-[1-(3-methoxyphenethyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H27)5-[4-[1-(3-hydroxyphenethyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H28)5-[4-[1-(2,4,6-trimethylbenzyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H29)4-[3-[5-[2-(pyridin-2-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-benzo[f]quinoxalin-2,3(1H,4H)-dionehydrochloride;

(Compound H30)5-[4-[5-[2-(6-methylpyridin-2-ylethyl)-1H-tetrazol-1-yl]-phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H31)5-[4-[(2-(3-fluorophenyl)ethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H32)5-[4-[(2-(2-methoxyphenyl)ethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H33)5-[4-[(2-(4-fluorophenyl)ethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H34)5-[4-[(2-(2-fluorophenyl)ethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H35)5-[4-[1-[2-(trifluoromethyl)benzyl]-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H36)5-[4-[2-[4-(trifluoromethyl)phenylethyl]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H37)5-[4-[2-(2,6-dimethylphenylethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H38)5-[4-[2-[3-(trifluoromethyl)phenylethyl]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H39)5-[4-[5-[2-(pyridin-2-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-one dihydrochloride;

(Compound H40)5-[4-(5-phenethyl-1H-tetrazol-1-yl)phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-one;

(Compound H41)5-[4-(2-phenethyl-1H-imidazol-1-yl)phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-onedihydrochloride;

(Compound H42)5-[4-[2-(3-methoxyphenethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H43)5-[4-[2-(3-hydroxyphenethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H44)3-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-tetrazol-5-yl]ethyl]benzonitrile;

(Compound H45)3-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-tetrazol-5-yl]ethyl]benzamide;

(Compound H46)5-[4-[5-[2-(2-methoxypyridin-3-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H47)5-[4-[5-[2-(dimethylamino)benzyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionemesylate;

(Compound H48)4-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl]phenyl]-1H-imidazol-2-yl]ethyl]benzonitrile;

(Compound H49)4-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl]phenyl]-1H-imidazol-2-yl]ethyl]benzamide;

(Compound H50)5-[4-(2-phenyl-1H-imidazol-1-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H51)5-[4-[2-(2-methoxyphenyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H52)2-[[2-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-imidazol-1-yl]methyl]benzonitrile;

(Compound H53)2-[[2-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-imidazol-1-yl]methyl]benzamide;

(Compound H54)2-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-imidazol-2-yl]ethyl]benzonitrile;

(Compound H55)2-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-imidazol-2-yl]ethyl]benzamide;

(Compound H56)3-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-imidazol-2-yl]ethyl]benzonitrile;

(Compound H57)3-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-imidazol-2-yl]ethyl]benzamide;

(Compound H58)3-[2-[1-[4-(2,4-dioxo-3,4-dihydro-1H-naphtho[1,2-b][1,4]diazepin-5(2H)-yl)phenyl]-1H-imidazol-2-yl]ethyl]benzamidehydrochloride;

(Compound H59)5-[4-[2-[4-(methylsulfonyl)phenethyl]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H60)5-[4-[2-(2-fluoro-3-methoxyphenethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H61)5-[4-[2-(3-methoxyphenethyl)-1H-imidazol-1-yl]phenyl]-5,8,9,10-tetrahydroindeno[4,5-b][1,4]diazepin-2,4(1H,3H)-dionehydrochloride;

(Compound H62)5-[4-[2-[2-(thiophen-3-yl)ethyl]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H63)5-[4-[1-(2-aminobenzyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H64)5-[3-methoxy-4-(1-phenethyl-1H-imidazol-2-yl)-phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H65)5-[3-hydroxy-4-(1-phenethyl-1H-imidazol-2-yl)-phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H66)5-[4-[2-[2-(furan-2-yl)ethyl]-1H-imidazol-1-yl]-phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H67)5-[4-[2-(2-fluorophenethyl)-1H-imidazol-1-yl]phenyl]-5,8,9,10-tetrahydroindeno[4,5-b][1,4]diazepin-2,4(1H,3H)-dione;

(Compound H68)5-[4-[2-(phenoxymethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H69)5-[4-[5-[2-methyl-2-(pyridin-2-yl)propyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H70)5-[4-[5-[2-(3-methoxypyridin-2-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H71)5-[4-[[2-(pyridin-2-yl)ethyl]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionedihydrochloride;

(Compound H72)5-[4-(5-phenyl-1H-imidazol-4-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H73)5-[4-[(5-phenylethyl)-1H-imidazol-4-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H74)5-[4-(4,4-dimethyl-2-phenethyl-4,5-dihydro-1H-imidazol-1-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H75)5-[4-[2-[(2-methoxyphenyl)amino]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H76)5-[4-[2-(phenylamino)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H77)5-[4-[1-[(6-methoxypyridin-2-yl)methyl]-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H78)5-[4-[1-[(6-hydroxypyridin-2-yl)methyl]-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;

(Compound H79)5-[4-[2-(3-fluorophenethyl)-1H-imidazol-1-yl]phenyl]-5,8,9,10-tetrahydroindeno[4,5-b][1,4]diazepin-2,4(1H,3H)-dionehydrochloride;

(Compound H80)5-[4-[2-[(phenylamino)methyl]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;

(Compound H81)3-[[2-[4-[2,4-dioxo-3,4-dihydro-1H-naphtho[2,1-b][1,4]diazepin-5-(2H)-yl]phenyl]-1H-imidazol-1-yl]methyl]benzonitrile;

(Compound H82)3-[[2-[4-[2,4-dioxo-3,4-dihydro-1H-naphtho[2,1-b][1,4]diazepin-5-(2H)-yl]phenyl]-1H-imidazol-1-yl]methyl]benzamide;and

(Compound H83)5-[4-[(2-(3-fluoro-2-methoxyphenyl)ethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride.

Note that the following shows specific examples of preferable compoundsand pharmaceutically acceptable salts thereof included in the compoundsrepresented by general formulas (AI) to (HII). However, a compound orpharmaceutically acceptable salt thereof that can be utilized as anactive ingredient in a medicament of the present invention is notlimited to them. More specifically, examples include:5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionepotassium salt;5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-one;5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-onesodium salt;5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;5-[3-(1H-tetrazol-5-yl)phenyl]-8,9,10,11-tetrahydronaphtho[2,1-b][1,4]diazepin-2,4(3H,5H)-dione;5-[3-(1H-tetrazol-5-yl)phenyl]-8,9,10,11-tetrahydronaphtho[2,1-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;4-[3-(1H-tetrazol-5-yl)phenyl]-1,4-dihydrobenzo[f]quinoxaline-2,3-dione;4-[3-(1H-tetrazol-5-yl)phenyl]-1,4-dihydrobenzo[f]quinoxaline-2,3-dionesodium salt; 4-[3-(1H-tetrazol-5-yl)phenyl]-1H-benzo[h]quinazolin-2-one;4-[3-(1H-tetrazol-5-yl)phenyl]-1H-benzo[h]quinazolin-2-one sodium salt;5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-[5-(2-methoxybenzyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-[5-(2-hydroxybenzyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-(5-phenethyl-1H-tetrazol-1-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[6-[5-(2-hydroxybenzyl)-1H-tetrazol-1-yl]pyridin-3-yl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-(2-phenethyl-1H-imidazol-1-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;5-[4-(1-phenethyl-1H-imidazol-2-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;5-[4-[1-(3-methoxyphenethyl)-1H-imidazol-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-[1-(3-hydroxyphenethyl)-1H-imidazole-2-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;5-[4-[(2-(3-fluorophenyl)ethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;5-[4-[2-(2,6-dimethylphenylethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;5-[4-[2-(3-methoxyphenethyl)-1H-imidazole-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;5-[4-[2-(3-hydroxyphenethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;5-[4-[5-[2-(dimethylamino)benzyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionemesylate;5-[4-[2-(3-methoxyphenethyl)-1H-imidazol-1-yl]phenyl]-5,8,9,10-tetrahydroindeno[4,5-b][1,4]diazepin-2,4(1H,3H)-dionehydrochloride;5-[4-[2-[2-(thiophen-3-yl)ethyl]-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;5-[4-[2-(2-fluorophenethyl)-1H-imidazol-1-yl]phenyl]-5,8,9,10-tetrahydroindeno[4,5-b][1,4]diazepin-2,4(1H,3H)-dione;5-[4-[2-(3-fluorophenethyl)-1H-imidazol-1-yl]phenyl]-5,8,9,10-tetrahydroindeno[4,5-b][1,4]diazepin-2,4(1H,3H)-dionehydrochloride;5-[4-[(2-(3-fluoro-2-methoxyphenyl)ethyl)-1H-imidazol-1-yl]phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionehydrochloride;2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamide;2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedihydrochloride; and2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedimethanesulfonate. Here, an active ingredient in a medicament of thepresent invention is not limited to the above specific compounds orpharmaceutically acceptable salts thereof.

Each compound or a pharmaceutically acceptable salt thereof moresuitable as an active ingredient in a medicament of the presentinvention is included in compounds or pharmaceutically acceptable saltsthereof represented by general formulas (AI) to (HII). Still morespecifically, examples include:5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt;5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione;2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamide;and2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedihydrochloride. Here, an active ingredient in a medicament of thepresent invention is not limited to the above specific compounds orpharmaceutically acceptable salts thereof.

The compounds represented by general formulas (AI) to (HII) may havestereoisomers such as cis/trans isomers, enantiomers, and/or racemates,all of which are included in the present invention.

In addition, the compounds represented by general formulas (AI) to (HII)may have one or two or more asymmetric carbon atoms depending on thekinds of substituent(s). Here, any enantiomers based on the asymmetriccarbon(s), any mixture of the enantiomers, racemates, diastereomersbased on the two or more asymmetric carbon atoms, or any mixture of thediastereomers, for instance, may be used as an active ingredient in amedicament of the present invention. When the compounds represented bygeneral formulas (AI) to (HII) contain a double bond and/or a ringstructure, a geometrical isomer(s) may be present. In addition togeometrical isomers in a pure form, a mixture of the geometrical isomersat any ratio may be used as an active ingredient in a medicament of thepresent invention.

As an active ingredient in a medicament of the present invention, it ispossible to use, in addition to the compounds represented by generalformulas (AI) to (HII), any acid adduct or any base adduct of thesecompounds. Examples of the acid adduct that can be used include, but arenot limited to, a mineral acid salt (e.g., hydrochloride, sulfate,nitrate) or an organic acid salt (e.g., methanesulfonate,p-toluenesulfonate, oxalate, malate). Examples of the base adductinclude, but are not limited to, a metal salt (e.g., a lithium salt, asodium salt, a potassium salt, a magnesium salt, or a calcium salt), anammonium salt, or an organic amine salt (e.g. a triethylamine salt or anethanolamine salt). Among these salts, it is preferable to use anypharmaceutically acceptable salt as an active ingredient in a medicamentof the present invention. Besides, it is possible to use, as an activeingredient in a medicament of the present invention, any hydrate orsolvate of each compound in a free form or in a salt form.

A medicament of the present invention may be used for preventing ortreating cough. Preferably, the medicament may be used for preventing ortreating acute cough, persistent cough, or chronic cough. Morepreferably, the medicament may be used for preventing or treatingchronic cough. A medicament of the present invention can elicit highefficacy on cough such as a disease responsible for chronic coughincluding dry cough (e.g., cough caused by cough variant asthma, atopiccough, cough caused by gastroesophageal reflux, chemical-induced cough,or allergic cough) or wet cough (e.g., cough caused by sinobronchialsyndrome, cough caused by chronic bronchitis, cough caused by chronicobstructive pulmonary disease, or cough caused by asthma). Each cough isindicated for a medicament of the present invention. However, theindication for a medicament of the present invention is not limited tothem.

Conventionally, treatment of dry cough, for instance, treatment of coughvariant asthma aims at enlarging the narrowed trachea and suppressingtracheal hypersensitivity. Examples of a therapeutic used include aninhaled steroid agent or a bronchodilator (e.g., a β2 stimulator).

However, the β2 stimulator, which is a bronchodilator, may have anadverse effect(s) such as tachycardia, tremor, and/or hypokalemia. Thus,it should be carefully administered to, for instance, patients withhypertension and/or patients with heart disease.

Meanwhile, a medicament of the present invention is presumed to exert noeffects on α1, β2, or M3 receptors, and should not exert any of theadverse effects caused by the existing bronchodilator (e.g., a β2stimulator). Thus, the medicament of the present invention can beexpected to be positively used for dry cough in the patients.

Conventionally, in treatment of wet cough, for instance, treatment ofbronchial asthma, airway inflammation and airway stenosis may be majortargets. Examples of a therapeutic used include an inhaled steroid agenthaving anti-inflammatory action. In addition, a bronchodilator (e.g., aβ2 stimulator or a theophylline sustained-release agent) or an allergicresponse-suppressing anti-inflammatory may be used in combination withthe inhaled steroid agent depending on the patient conditions.

In the above treatment, the bronchodilator (β2 stimulator) fails to haveanti-inflammatory action, and can thus be used in combination with aninhaled steroid agent. Meanwhile, a bronchodilator (β2 stimulator) and amedicament of the present invention should be used in combination to beable to treat wet cough.

The inhaled steroid agent may have an adverse effect(s) such asdysphonia involving, for instance, hoarse voice. A medicament of thepresent invention can avoid the adverse effect(s) and should be able totreat dry cough such as cough variant asthma.

Specifically, a medicament of the present invention is presumed to exertno effects on α1, β2, or M3 receptors, and should not augment adverseeffects (e.g., tachycardia, tremor, and/or hypokalemia) caused by theexisting bronchodilator (e.g., a β2 stimulator). Thus, the medicament ofthe present invention can be expected to be positively used for wetcough in, for instance, patients with hypertension and/or patients withheart disease.

Any compound suitable as an active ingredient in a medicament of thepresent invention elicits a dose-dependent, potent antitussive effect.

For instance, any compound suitable as an active ingredient in amedicament of the present invention can elicit substantially the sameantitussive effect as of dihydrocodeine, a central nervous system actingantitussive agent. In addition, the compound can inhibit only coughreflux increased by LPS stimulation in cough reflux caused by citricacid stimulation when administered at a low dose (0.3 mg/kg) to airwayinflammation model animals (e.g., airway inflammation model mice), whichare chronic cough model animals, and does not affect any cough reflux(the level corresponding to cough reflux caused by citric acidstimulation in normal mice) caused by citric acid stimulation alone. Inaddition, the compound has elicited medicament efficacy upon not onlyoral administration, but also local application using a nebulizer.

Further, the compound can inhibit only cough reflux increased due toairway inflammation accompanied by eosinophil infiltration induced byOVA sensitization in cough reflux caused by citric acid stimulation whenadministered at a low dose (1.0 mg/kg) to airway inflammation modelanimals (e.g., an antigen OVA-sensitized guinea pigs (allergic cough andatopic cough models)), which are chronic cough model animals, and doesnot affect any cough reflux (the level corresponding to cough refluxcaused by citric acid stimulation in normal guinea pigs) caused bycitric acid stimulation alone.

Collectively, as one embodiment, any compound suitable as an activeingredient in a medicament of the present invention has no problem ofwater solubility, the osmotic pressure and pH of solution administered,other stimulant properties, etc., and does not have a risk of stoppingcough that is necessary as biological defense and should not be stoppedessentially as caused by a central nervous system acting medicament.Hence, the medicament of the present invention can exert a betterperipheral antitussive effect in humans suffering from chronic coughthan healthy individuals.

A medicament of the present invention may be administered orally orparenterally. A medicament of the present invention may be produced, bya regular procedure in the art of formulation, as a medicament insuitable dosage forms including tablets, granules, powders, capsules,suspensions, inhalants, inhalation powders, inhalation solutions,inhalation aerosols, ointments, creams, gels, compresses, patches,liniments, tapes, poultices, injections, or suppositories.

These formulations can be produced by common techniques. In the case oftablets, for instance, common excipients, disintegrants, binders,lubricants, and/or pigments may be used. Examples of the excipientsinclude lactose, D-mannitol, crystalline cellulose, and glucose.Examples of the disintegrants include starch and carboxymethylcellulosecalcium (CMC-Ca). Examples of the lubricants include magnesium stearateand talc. Examples of the binders include hydroxypropyl cellulose (HPC),gelatin, and polyvinylpyrrolidone (PVP).

A solvent, a stabilizer, a solubilizer aid, a suspending agent, anemulsifier, a soothing agent, a buffer, and/or a preservative, forinstance, are used to adjust an injection. Those skilled in the art canselect, if appropriate, these additives for formulation and a processfor preparing the formulation.

Examples of the inhalants for parenteral administration includeaerosols, powders for inhalation, liquids for inhalation (e.g.,solutions for inhalation, suspensions for inhalation), or capsuleinhalants. The liquids for inhalation may be in a form used whiledissolved or suspended in water or other suitable solvents when used.Each inhalant may be applied using a suitable inhalant container. Forinstance, when liquid for inhalation is administered, a spray (e.g., anatomizer, a nebulizer) may be used and when powder for inhalation isadministered, an inhalant applicator for powder agent may be used.

These inhalants can be produced in accordance with publicly knownprocedures. For instance, any of the compounds represented by generalformulas (AI) to (HII) may be made powder or liquid, which is thenformulated in an inhalation spray preparation or a carrier and filled ina suitable inhalant container for production. When any of the compoundsrepresented by general formulas (AI) to (HII) is made powder, a commonprocedure is used to make the compound powder. For instance, thecompound is made fine powder with lactose, starch, and/or magnesiumstearate to prepare a homogenous mixture or is granulated therewith toprepare a powder agent. In addition, when any of the compoundsrepresented by general formulas (AI) to (HII) is made liquid, thecompound, for instance, may be dissolved in a liquid carrier such aswater, saline, or an organic solvent. As the spray preparation, it ispossible to use a conventionally known spray preparation such asalternative freon, a liquefied gas spray preparation (e.g.,fluorohydrocarbon, liquefied petroleum, diethyl ether, dimethyl ether),compressed gas (e.g., soluble gas (e.g., carbon dioxide, nitrous oxidegas)), or insoluble gas (e.g., nitrogen gas).

Each inhalant may be optionally combined, if appropriate, with anadditive(s). Any commonly used additive(s) may be allowed as theadditive(s). Examples of the additives that can be used include solidexcipients (e.g., sucrose, lactose, glucose, mannitol, sorbitol,maltose, cellulose), liquid excipients (e.g., propylene glycol), binders(starch, dextrin, methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyethylene glycol, white sugar), lubricants (e.g.,magnesium stearate, light silicic anhydride, talc, sodium laurylsulfate), flavoring agents (e.g., citric acid, menthol, a glycyrrhizinammonium salt, glycine, orange powder), preservatives (e.g., sodiumbenzoate, sodium bisulfite, methyl paraben, propyl paraben), stabilizers(e.g., citric acid, sodium citrate), suspending agents or emulsifiers(e.g., methyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol,lecithin, sorbitan trioleate), dispersants (e.g., a surfactant),solvents (e.g., water), tonicity agents (e.g., sodium chloride,concentrated glycerin), pH modifiers (e.g., hydrochloric acid, sulfuricacid), solubilizers (e.g., ethanol), antiseptics (e.g., benzalkoniumchloride, paraben), coloring agents, buffering agents (e.g., sodiumphosphate, sodium acetate), thickeners (e.g., kariboxy vinyl polymer,etc.), and/or absorption promoters. In the case of liquid forinhalation, for instance, the liquid may be prepared by optionallyselecting, if appropriate, an antiseptic, a coloring agent, a bufferingagent, a tonicity agent, a thickener, and/or an absorption promoter. Inaddition, in the case of powder for inhalation, for instance, the powdermay be prepared by optionally selecting, if appropriate, a lubricant, abinder, an excipient, a coloring agent, an antiseptic, and/or anabsorption promoter (e.g., a bile acid salt, chitosan).

Further, to give sustained release property to the compounds representedby general formulas (AI) to (HII), each inhalant may contain abiodegradable polymer. Examples of the biodegradable polymer includefatty acid ester polymers or copolymers thereof, polyacrylic esters,polyhydroxybutyric acids, polyalkylene oxalates, polyorthoesters,polycarbonates, and polyamino acids. The polymers may be used singly, ormore kinds of them may be mixed and used. In addition, a phospholipidsuch as egg yolk lecithin, chitosan, or the like may be used. Examplesof the fatty acid ester polymers or copolymers thereof includepolylactic acid, polyglycolic acid, polycitric acid, polymalic acid, anda lactic acid-glycolic acid copolymer. They may be used singly, or morekinds of them may be mixed and used. Other examples include polyα-cyanoacrylate, poly β-hydroxybutyric acid, polytrimethyleneoxate,polyorthoester, polyorthocarbonate, polyethylene carbonate, polyγ-benzyl-L-glutamic acid, and poly L-alanine. They may be used singly,or more kinds of them may be mixed and used. Preferred is polylacticacid, polyglycolic acid, or a lactic acid-glycolic acid copolymer. Morepreferred is a lactic acid-glycolic acid copolymer. In addition, abiodegradable polymer such as a lactic acid-glycolic acid copolymer maybe used to prepare a medicament-encapsulating microsphere or nanosphere.

Ointments may be produced by publicly known or commonly usedformulation. For instance, one or more active substances are ground ormelted into a base for production and preparation. The ointment base maybe selected from those publicly known or commonly used. Examples includehigher fatty acids or higher fatty acid esters (e.g., adipic acid,myristic acid, palmitic acid, stearic acid, oleic acid, adipic acidester, myristic acid ester, palmitic acid ester, stearic acid ester,oleic acid ester), waxes (e.g., beeswax, whale wax, ceresin),surfactants (e.g., polyoxyethylene alkyl ether phosphate), higheralcohols (e.g., cetanol, stearyl alcohol, cetostearyl alcohol, etc.),silicone oil (e.g., dimethylpolysiloxane), hydrocarbons (e.g.,hydrophilic petrolatum, white petrolatum, purified lanolin, liquidparaffin), glycols (e.g., ethylene glycol, diethylene glycol, propyleneglycol, polyethylene glycol, macrogol), vegetable oils (e.g., castoroil, olive oil, sesame oil, turpentine oil), animal oils (e.g., minkoil, egg yolk oil, squalane, squalene), water, absorption enhancers, oranti-rash agents. Those selected from them may be used singly, or two ormore kinds of them may be mixed and used. It is possible to furthercontain, for instance, a moisturizer, a preservative, a stabilizer, anantioxidant, and/or a flavoring agent.

Gels may be produced by publicly known or commonly used formulation. Forinstance, one or more active substances are melted into a base forproduction and preparation. The gel base may be selected from thosepublicly known or commonly used. Examples include lower alcohols (e.g.,ethanol, isopropyl alcohol), gelling agents (e.g.,carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,ethylcellulose), neutralizing agents (e.g., triethanolamine,diisopropanolamine), surfactants (e.g., polyethylene glycolmonostearate), gums, water, absorption enhancers, or anti-rash agents.Those selected from them may be used singly, or two or more kinds ofthem may be mixed and used. It is possible to further contain, forinstance, a preservative, an antioxidant, and/or a flavoring agent.

Creams may be produced by publicly known or commonly used formulation.For instance, one or more active substances are melted or emulsifiedinto a base for production and preparation. The cream base may beselected from those publicly known or commonly used. Examples includehigher fatty acid esters, lower alcohols, hydrocarbons, polyhydricalcohols (e.g., propylene glycol, 1,3-butylene glycol), higher alcohols(e.g., 2-hexyldecanol, cetanol), emulsifiers (e.g., polyoxyethylenealkyl ethers, fatty acid esters), water, absorption enhancers, oranti-rash agents. Those selected from them may be used singly, or two ormore kinds of them may be mixed and used. It is possible to furthercontain, for instance, a preservative, an antioxidant, and/or aflavoring agent.

Poultices may be produced by publicly known or commonly usedformulation. For instance, one or more active substances are melted intoa base to prepare a kneaded material, which is then applied and extendedon a support for production. The poultice base may be selected fromthose publicly known or commonly used. Examples include thickeners(e.g., polyacrylic acid, polyvinylpyrrolidone, gum arabic, starch,gelatin, methylcellulose), wetting agents (e.g., urea, glycerin,propylene glycol), fillers (e.g., kaolin, zinc oxide, talc, calcium,magnesium), water, dissolution aids, tackifiers, or anti-rash agents.Those selected from them may be used singly, or two or more kinds ofthem may be mixed and used. It is possible to further contain, forinstance, a preservative, an antioxidant, and/or a flavoring agent.

Patches may be produced by publicly known or commonly used formulation.For instance, one or more active substances are melted into a base,which is then applied and extended on a support for production. The basefor patches may be selected from those publicly known or commonly used.Examples include polymer bases, oils and fats, higher fatty acids,tackifiers, or anti-rash agents. Those selected from them may be usedsingly, or two or more kinds of them may be mixed and used. It ispossible to further contain, for instance, a preservative, anantioxidant, and/or a flavoring agent.

Liniments may be produced by publicly known or commonly usedformulation. For instance, one or more active substances may bedissolved, suspended, or emulsified into one or two or more kindsselected from, for instance, water, alcohol (e.g., ethanol, polyethyleneglycol), higher fatty acid, glycerin, a soap, an emulsifier, or asuspending agent. Then, each liniment is so produced and prepared. It ispossible to further contain, for instance, a preservative, anantioxidant, and/or a flavoring agent.

The dose of a medicament of the present invention is not particularlylimited, and the medicament may be typically administered to an adultsuch that a daily dose as an active ingredient amount in an inhalant,inhalation powder, inhalation liquid, or inhalation aerosol is fromabout 0.01 μg to 100 mg and preferably from 0.3 μg to 10 mg; a dailydose as an active ingredient amount in an ointment, cream, gel,compress, patch, liniment, tape, or cataplasm is from about 0.01 mg to1000 mg; a daily dose as an active ingredient amount in an injection isfrom about 0.01 mg to 100 mg; and a daily dose by orally administrationis somewhat from 0.01 mg to 2000 mg. Here, the dose is not limited tothe above-described doses, and can be changed depending on the ageand/or symptoms, etc.

A medicament of the present invention may be used in combination withanother agent useful for treating or preventing a variety of cough.Individual ingredients in such a combination may be administered atdifferent time points or the same time during a treatment or preventionperiod and may be administered as separate formulations or a singleformulation. Thus, the present invention should be interpreted toinclude any of simultaneous administration or administration atdifferent time points. Thus, administration in the present inventionshould be construed in this way. The scope of the above combinationbetween a medicament of the present invention and another agent usefulfor treating or preventing a variety of cough encompasses, in principle,combinations with any pharmaceutical formulation useful for treating orpreventing a variety of cough described above.

Various forms of each formulation among the combination formulations inthe present invention can be selected and each formulation can beproduced in the same fashion as for the above formulations. In addition,in the case of a combination comprising a medicament of the presentinvention and a therapeutic or prophylactic for a variety of cough, askilled artisan can easily produce the combination in accordance with acommon procedure or a conventional technique.

The above combinations include not only a combination between amedicament of the present invention and another active substance, butalso a combination with two or more additional active substances. Manyexamples exist for combinations between a medicament of the presentinvention and one or two or more active substances selected from variouscough therapeutics or prophylactics described above.

Examples of the medicament used in combination with a medicament of thepresent invention include steroids, β2 agonists, muscarinic receptorantagonists, antihistamines, antiallergic agents, bronchodilators,leukotriene synthesis inhibitors, prostaglandins, leukotriene receptorantagonists, additional antitussives, and expectorants. Among them, itis preferable to use a combination with an antihistamine or anantiallergic agent and to use a combination with, for instance, asteroid, a β2 agonist, or a muscarinic receptor antagonist effective inwet cough. Further, a medicament of the present invention may be used incombination with a herbal medicine.

Examples of the steroid include: an external medicine (e.g., clobetasolpropionate, diflorazone acetate, fluocinonide, mometasone furoate,betamethasone dipropionate, betamethasone butyrate propionate,betamethasone valerate, difluprednate, pudesonide, diflucortronvalerate, amcinonide, halcinonide, dexamethasone, dexamethasonepropionate, dexamethasone valerate, dexamethasone acetate,hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone butyratepropionate, deprodone propionate, prednisolone valerate acetate,fluocinolone acetonide, beclomethasone propionate, triamcinoloneacetonide, flumethasone pivalate, alclomethasone propionate, clobetasonebutyrate, prednisolone, peclomethasone propionate, fludroxycortide); aninternal medicine or injection (e.g., cortisone acetate, hydrocortisone,hydrocortisone sodium phosphate, hydrocortisone sodium succinate,fludrocortisone acetate, prednisolone, prednisolone acetate,prednisolone sodium succinate, prednisolone butyl acetate, prednisolonesodium phosphate, halopredone acetate, methyl prednisolone, methylprednisolone acetate, methylprednisolone sodium succinate,triamcinolone, triamcinolone acetate, triamcinolone acetonide,dexamethasone, dexamethasone acetate, dexamethasone sodium phosphate,dexamethasone palmitate, paramethasone acetate, betamethasone); or aninhalant (e.g., beclomethasone propionate, fluticasone propionate,budesonide, flunisolide, triamcinolone, ST-126P, ciclesonide,dexamethasone paromithionate, mometasone furan carbonate, plasteronesulfonate, deflazacort, methylprednisolone suleptanate,methylprednisolone sodium succinate).

Examples of the (2 agonist include formoterol, salmeterol, carmoterol,indacaterol, bilanterol, alformoterol, bambuterol, isoproterenol,milbeterol, clenbuterol, olodaterol, fenoterol, salbutamol,levalbuterol, procaterol, terbutaline, pyrbuterol, procaterol,metaproterol, bitolterol, ritodrine, or albuterol.

Examples of the muscarinic receptor antagonist include tiotropium,ipratropium, flutropium, oxitropium, acridinium, darotropium,glycopyrrolate, or umecridinium.

Examples of the antihistamine include diphenhydramine, diphenylpyralinehydrochloride, diphenylpyraline teocoleate, clemastine fumarate,dimenhydrinate, dl-chlorpheniramine maleate, d-chlorpheniramine maleate,triprolidine hydrochloride, promethazine hydrochloride, alimemazinetartrate, isotipendil hydrochloride, homochlorcyclidine hydrochloride,hydroxyzine, cyproheptadine hydrochloride, levocabastine hydrochloride,astemizole, bepotastine, desloratadine, TAK-427, ZCR-2060, NIP-530,mometasone furoate, mizolastine, BP-294, andlast, auranofin, orakrivastin.

Examples of the antiallergic agent include: a chemical mediator releaseinhibitor (e.g., sodium cromoglycate, tranilast, amlexanox, repirinast,ibudilast, pemirolast potassium, dazanolast, nedocromil, cromoglycate,israpafant); a histamine antagonist (e.g., ketotifen fumarate,azelastine hydrochloride, oxatomide, mequitazine, terfenadine,emedastine fumarate, epinastine hydrochloride, ebastine, cetirizinehydrochloride, olopatadine hydrochloride, loratadine, fexofenadine); athromboxane synthase inhibitor (e.g., osagrel hydrochloride, imitrodastsodium); a thromboxane antagonist (e.g., seratrodast, ramatroban,domitroban calcium hydrate, KT-2-962); or a Th2 cytokine inhibitor(e.g., suplatast tosilate).

Examples of the bronchodilator include: a xanthine derivative (e.g.,aminophylline, theophylline, doxophylline, sipamphylline, diprofylline,proxyphylline, cholinetheophylline); a sympathetic stimulant (e.g.,epinephrine, ephedrine hydrochloride, dl-methylephedrine hydrochloride,methoxyphenamine hydrochloride, isoproterenol sulfate, isoproterenolhydrochloride, orciprenaline sulfate, chlorprenaline hydrochloride,trimethokinol hydrochloride, salbutamol sulfate, terbutaline sulfate,hexoprenaline sulfate, tulobuterol hydrochloride, procaterolhydrochloride, fenoterol hydrobromide, formoterol fumarate, clenbuterolhydrochloride, mabuterol hydrochloride, salmeterol xinafoate,R,R-formoterol, tulobuterol, pyrbuterol hydrochloride, ritodrinehydrochloride, bambuterol, dopexamine hydrochloride, meradrine tartrate,AR-C68397, levosalbutamol, KUR-1246, KUL-7211, AR-C89855, S-1319); or aparasympathetic blocker (e.g., ipratropium bromide, flutropium bromide,oxitropium bromide, cimetropium bromide, temiverine, tiotropium bromide,revatropate)

Examples of the leukotriene synthesis inhibitor include auranofin,progamatasin maleate, L-674636, A-81834, UPA-780, A-93178, MK-886,REV-5901A, SCH-40120, MK-591, Bay-x-1005, Bay-y-1015, DTI-0026,amlexanox, or E-6700.

Examples of the prostaglandin compound include an agonist or antagonistfor PGE2EP1 receptor, PGE2EP2 receptor, PGE2EP3 receptor, or PGE2EP4receptor; an agonist or antagonist for PGD2 receptor or CRTH2 receptor;an agonist or antagonist for PGFFP receptor; an agonist or antagonistfor PGIIP receptor; or an agonist or antagonist for TX receptor.

Examples of the leukotriene receptor antagonist include pranlukasthydrate, montelukast, zafirlukast, seratrodast, MCC-847, KCA-757,CS-615, YM-158, L-740515, CP-195494, LM-1484, RS-635, A-93178, S-36496,BIIL-284, or ONO-4057.

Examples of the additional antitussive include codeine phosphate,dihydrocodeine phosphate, oxymethebanol, dextromethorphan hydrobromide,pentoxiverine citrate, dimemorphane phosphate, oxeradine citrate,cloperastine, benproperin phosphate, clofedanol hydrochloride, hominobenhydrochloride, noscapine, tipemidine hibenzanate, epradinonehydrochloride, or plantago herb extract.

Examples of the expectorant include foeniculated ammonia spirit, sodiumbicarbonate, potassium iodide, bromhexine hydrochloride, cherry barkextract, carbocisteine, fudostein, ambroxol hydrochloride, ambroxolhydrochloride sustained-release agent, methyl cysteine hydrochloride,acetylcysteine, L-ethylcysteine hydrochloride, or tyloxapol.

The present invention has the following aspects.

<1a> A method for preventing or treating cough, the method comprisingadministering, to a subject (e.g., a mammal comprising a human) in needthereof, a therapeutically effective amount of a compound having P2X4receptor antagonistic action, a tautomer, stereoisomer, orpharmaceutically acceptable salt of the compound, or a hydrate orsolvate thereof.

<2a> The method according to <1a>, wherein the cough is acute cough,persistent cough, or chronic cough.

<3a> The method according to <2a>, wherein the cough is chronic cough.

<4a> The method according to <1a>, wherein the cough is dry cough thatis cough caused by cough variant asthma, atopic cough, cough caused bygastroesophageal reflux, chemical-induced cough, or allergic cough.

<5a> The method according to <4a>, wherein the cough is dry cough thatis cough caused by cough variant asthma, atopic cough, or allergiccough.

<6a> The method according to <1a>, wherein the cough is wet cough thatis cough caused by sinobronchial syndrome, cough caused by chronicbronchitis, cough caused by chronic obstructive pulmonary disease, orcough caused by asthma.

<7a> A method for peripheral cough suppression of dry cough, the methodcomprising administering, to a subject (e.g., a mammal comprising ahuman) in need thereof, a therapeutically effective amount of a compoundhaving P2X4 receptor antagonistic action, a tautomer, stereoisomer, orpharmaceutically acceptable salt of the compound, or a hydrate orsolvate thereof.

<8a> The method according to <7a>, which is selective to the peripheralcough suppression of dry cough.

<9a> The method according to <7a> or <8a>, wherein the dry cough iscough caused by cough variant asthma, atopic cough, or allergic cough.

<10a> The method according to any one of <1a> to <9a>, wherein thecompound having P2X4 receptor antagonistic action is a compoundrepresented by any one of general formulas (AI) to (HII) (where specificexamples and preferable examples of the compound represented by any oneof general formulas (AI) to (HII) are as described herein).

<1b> A compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use in prophylaxis or treatment of cough.

<2b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <1b>, wherein the coughis acute cough, persistent cough, or chronic cough.

<3b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <2b>, wherein the coughis chronic cough.

<4b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <1b>, wherein the coughis dry cough that is cough caused by cough variant asthma, atopic cough,cough caused by gastroesophageal reflux, chemical-induced cough, orallergic cough.

<5b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <4b>, wherein the coughis dry cough that is cough caused by cough variant asthma, atopic cough,or allergic cough.

<6b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <1b>, wherein the coughis wet cough that is cough caused by sinobronchial syndrome, coughcaused by chronic bronchitis, cough caused by chronic obstructivepulmonary disease, or cough caused by asthma.

<7b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <1b>, wherein theprophylaxis or treatment of cough is peripheral cough suppression of drycough.

<8b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <7b>, which is selectiveto peripheral cough suppression of dry cough.

<9b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to <7b> or <8b>, whereinthe dry cough is cough caused by cough variant asthma, atopic cough, orallergic cough.

<10b> The compound having P2X4 receptor antagonistic action, a tautomer,stereoisomer, or pharmaceutically acceptable salt of the compound, or ahydrate or solvate thereof for use according to any one of <1b> to <9b>,wherein the compound having P2X4 receptor antagonistic action is acompound represented by any one of general formulas (AI) to (HII) (wherespecific examples and preferable examples of the compound represented byany one of general formulas (AI) to (HII) are as described herein).

<1c> Use of a compound having P2X4 receptor antagonistic action, atautomer, stereoisomer, or pharmaceutically acceptable salt of thecompound, or a hydrate or solvate thereof in the manufacture of amedicament for preventing or treating cough.

<2c> The use according to <1c>, wherein the cough is acute cough,persistent cough, or chronic cough.

<3c> The use according to <2c>, wherein the cough is chronic cough.

<4c> The use according to <1c>, wherein the cough is dry cough that iscough caused by cough variant asthma, atopic cough, cough caused bygastroesophageal reflux, chemical-induced cough, or allergic cough.

<5c> The use according to <4c>, wherein the cough is dry cough that iscough caused by cough variant asthma, atopic cough, or allergic cough.

<6c> The use according to <1c>, wherein the cough is wet cough that iscough caused by sinobronchial syndrome, cough caused by chronicbronchitis, cough caused by chronic obstructive pulmonary disease, orcough caused by asthma.

<7c> Use of a compound having P2X4 receptor antagonistic action, atautomer, stereoisomer, or pharmaceutically acceptable salt of thecompound, or a hydrate or solvate thereof for the manufacture of aperipheral antitussive agent for dry cough.

<8c> Use according to <7c>, wherein the peripheral antitussive agent fordry cough is a medicament selective to peripheral cough suppression ofdry cough.

<9c> The use according to <7c> or <8c>, wherein the dry cough is coughcaused by cough variant asthma, atopic cough, or allergic cough.

<10c> The use according to any one of <1c> to <9c>, wherein the compoundhaving P2X4 receptor antagonistic action is a compound represented byany one of general formulas (AI) to (HII) (where specific examples andpreferable examples of the compound represented by any one of generalformulas (AI) to (HII) are as described herein).

As one aspect, the “dry cough” is a counter concept of “wet cough”. Asanother aspect, the “peripheral cough suppression” is a counter conceptof “central cough suppression”. As used herein, the expression“selective” to A includes that efficacy and effects on A is relativelysuperior over efficacy and effects on the others, and indicates aconcept that may include the idea where there are efficacy and effectson just A and there are neither efficacy nor effects on the others.Accordingly, as used herein, the expression “selective to peripheralcough suppression of dry cough” encompasses that the effectiveness on“dry cough” is relatively superior over the effectiveness on “wetcough”, and also encompasses that there is effectiveness on only “drycough” and there is no effectiveness on “wet cough” and includes thatthe effects on “peripheral cough suppression” is relatively superiorover the effects on “central cough suppression” and also represents aconcept that may include the idea where there are effects on just“peripheral cough suppression” and there are no effects on “centralcough suppression”.

EXAMPLES

Hereinafter, the present invention will be further specificallydescribed by using Examples. However, the scope of the present inventionis not limited to the following Examples.

In the following Examples, P2X4 antagonists were used, including:5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionesodium salt (WO2010/093061, a sodium salt of the compound of Example 1:hereinafter referred to as “compound A”);5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione(WO2013/105608, the compound of Example 48: hereinafter referred to as“compound B”);5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione(WO2013/105608, the compound of Example 2: hereinafter referred to as“compound C”);2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedihydrochloride (WO2015/005467, the compound of Example 15: hereinafterreferred to as “compound D”); and other compounds shown below.

Example 1

To Measure P2X4 Receptor Antagonistic Action of Compound as ActiveIngredient of the present invention.

(Test Protocol)

The P2X4 receptor antagonistic action of a compound as an activeingredient of the present invention was measured. An ATP receptor (humanP2X4) was introduced in 1321N1 cells, which were then used as a systemin which P2X4 receptor was expressed stably. The P2X4receptor-expressing cells were seeded on a 96-well plate, were culturedfor 24 h under conditions at 37° C. and 5% C02, and were then used forcalcium measurement. Fura-2AM, which is a calcium fluorescenceindicator, was dissolved in an extracellular solution for calciumimaging and applied to the seeded cells. Then, the cells were allowed tostand at room temperature for 45 min. In this way, the Fura-2AM wastaken up in the cells. A micro plate reader EnVision (PerkinElmer) wasused for the measurement. Light emitted from a xenon lamp was made topass through a 340-nm or 380-nm filter, and F340 or F380, which is510-nm fluorescence emitted when the cells were irradiated, wereobserved. Then, a change in the ratio value F340/F380 was an index forthe intracellular calcium change. The measurement was carried out byadding ATP at the final concentration of 1 μM to each well and byrecording, over time, the ATP-induced intracellular calcium response.The inhibitory activity of each test substance was measured byconducting 15-min pretreatment with each test substance before ATPapplication, and was calculated while compared to the case of theabsence of the test substance. Table 131 below shows the results.

(Test Results)

TABLE 131 Test substance IC50 (μM) Compound A2 (Compound A) 0.53Compound A17 0.27 Compound A21 0.91 Compound A23 0.49 Compound B2 0.36Compound C2 0.57 Compound D2 0.33

Example 2

To Produce Model Mice with Chronic Cough Caused by Airway Inflammation.

Model mice with chronic cough caused by airway inflammation (referred toas “airway inflammation model mice”) were produced.

The airway inflammation model mice were produced while the mice werenasally instilled with lipopolysaccaride (LPS:1 μg/100 μL) daily for 3days under diethyl ether inhalation anesthesia.

In addition, experiments for evaluating medicament efficacy on theairway inflammation model mice were conducted at 24 h after the finalLPS administration.

Example 3

To Test Antitussive Action of Compound A

To test the presence or absence of antitussive action of compound A,mice that had orally received purified water or compound A in an amountof 0.3, 1, 3, or 10 mg/kg were stimulated with citric acid using anebulizer at 1 h after the administration to induce cough reflux. Inthis way, the effects were investigated.

Note that, as used herein, mice that have been given neitheradministration nor treatment are referred to as “pretreatment mice”;mice, namely pretreatment mice that have received purified water arereferred to as “control group mice”; and mice, namely pretreatment micethat have received a test subject compound are referred to as “testgroup mice”.

Citric acid stimulation-induced cough reflux was measured by thefollowing procedure.

At this time, ICR strain mice were used as the mice and 0.25 M citricacid was used as the citric acid.

(Cough Reflux-Measuring Procedure)

Cough reflux is induced by inhalation of (in the case of mice, 0.1 M or0.25 M and in the case of guinea pigs, 0.25 M or 0.5 M) citric acid bymice or guinea pigs under non-anesthesia conditions. The citric acid ismade aerosol by using an ultrasonic nebulizer (NE-U17: OMRONCorporation), and is inhaled while the air is supplied with anartificial respirator (SN-480-7: Shinano Seisakusho). The citric acidaerosol has an average particle size of from 1 to 8 μm, and theartificial respirator is used to supply the air at a one-timeventilation volume of 6 mL, a frequency of 30 times per min, and aninhalation period of 3 min.

The respiration and the cough reflux are measured in accordance with thebody-plethysmograph method. The plethysmograph used includes: aplastic-made, cylindrical cylinder part in which the trunk of each mouseor guinea pig is housed; and a cap part that covers the head portion(any plastic-made cylinder is allowed as long as each experimentalanimal can be put in; in the case of the mouse, for instance, the partwith a diameter of 4 cm and a length of 7 cm was used). An exhaust holeis created at an upper cylinder portion so as to be able to connect, viaa silicon tube, to a respiratory flow meter (TP-602T: NIHON KOHDENCORPORATION). To tightly seal the inside of the cylinder, a rubber orcelluloid collar is attached to the neck of each animal, and the capcovering the whole head is used to fix them. The head-attached cap parthas an exhaust port and an inhalation port created for inhalation of acough-inducing substance. In addition, a screw-type lid is attached to atail portion of the cylinder so as to move in or out each experimentalanimal. Each mouse is put in the cylinder, allowed to play for at least30 min, adapted to an experimental environment, and then subjected tothe experiment. The respiration is recorded in a PC (IdeaPad 300:Lenovo) for measurement by measuring, as a change in volume of thecylinder, the chest movement of each experimental animal in the cylinderby using a PowerLab (ML826 PowerLab 2/26: AD Instruments) via arespiratory flow meter. When a cough is induced, the chest of theexperimental animal is moved vigorously, which causes an instantaneouslarge volume change in the cylinder. This change is recorded using therespiratory flow meter. This frequency is recorded to measure the numberof coughs. The data is analyzed by LabChart version 8 (ADInstruments).In addition, immediately before inhalation of citric acid, therespiratory frequency per 15 sec is measured.

(Test Results)

FIGS. 1 and 2 show the results obtained.

The pre group in FIG. 1 shows the number of coughs after pretreatmentmice were stimulated with 0.25 M citric acid. The post group in FIG. 1shows the number of coughs after the control group mice in whichpurified water had been orally administered beforehand (at 1 h beforecitric acid administration) to the pretreatment mice or the test groupmice in which 0.3, 1, 3, or 10 mg/kg of compound A had been orallyadministered beforehand (at 1 h before citric acid administration) tothe pretreatment mice were stimulated with 0.5 M citric acid.

Here, FIG. 2 shows an inhibition rate while the rate obtained from theresults (FIG. 1 ) of this Example was 0% when the number of coughs wasneither increased nor decreased and the rate was 100% when the number ofcoughs was 0.

Compound A inhibited citric acid-induced cough in a dose-dependentmanner, and a significant inhibitory action was exhibited at 1 mg/kg orhigher.

Example 4

To Measure Antitussive Efficacy of Dihydrocodeine

Meanwhile, to compare compound A and dihydrocodeine, the control groupmice and the test group mice in which 10 mg/kg of dihydrocodeine hadbeen orally administered to pretreatment mice were tested bysubstantially the same procedure as of Example 3. At that time, ICRstrain mice were used as the mice. FIG. 3 shows the results.

(Test Results)

In a case in which 1 h after administration of purified water ordihydrocodeine, cough was triggered with 0.25 M citric acid by using anebulizer, the cough inhibition rate was comparable between compound Aand the same dose of dihydrocodeine.

Example 5

Effects of Compound A on Chronic Cough in Airway Inflammation Model MiceUsed.

FIG. 4 shows the results of using airway inflammation model mice toinvestigate medicament efficacy of compound A on chronic cough.

(Test Results)

Airway inflammation model mice were used to induce cough reflux bysubstantially the same procedure as of Example 3.

At this time, ICR strain mice were used for producing the airwayinflammation model mice and 0.1 M citric acid was used as the citricacid.

Compared to a case where pretreatment mice (pre1 of (a), (b), (c), and(d) in FIG. 4 ) were stimulated with 0.1 M citric acid to induce coughreflux, a case of mice (hereinafter, herein referred to as “sham groupmice”; (a) and (b) in FIG. 4) where the pretreatment mice were nasallyinstilled with saline instead of LPS in Example 2 and then stimulatedwith 0.1 M citric acid had no observed change in the number of coughs(pre2 of (a) and (b) in FIG. 4 ).

By contrast, when airway inflammation model mice (hereinafter, hereinreferred to as “airway inflammation group mice”; (c) and (d) in FIG. 4 )produced from the pretreatment mice by the procedure in Example 2 werestimulated with 0.1 M citric acid, an increase in cough response wasobserved (pre2 of (c) and (d) in FIG. 4 ).

When 0.3 mg/kg of compound A was orally administered beforehand (at 1 hbefore citric acid stimulation) to the airway inflammation group micebeing sensitive to this cough stimulation, the cough response increaseddue to airway inflammation was inhibited completely (post of (d) in FIG.4 ). On the contrary, when 0.3 mg/kg of compound A was orallyadministered beforehand (at 1 h before citric acid stimulation) to thesham group mice, a change in the number of coughs was unobserved (postof (b) in FIG. 4 ).

Thus, 0.3 mg/kg of compound A did not elicit any significant medicamentefficacy when the sham group mice were examined (when pre2 and post inFIG. 4(b) were compared) (0.3 mg/kg of compound A did not elicit anysignificant medicament efficacy in the examination of Example 3). Thishas revealed that cough necessary for biological defense (0.1 M citricacid-induced cough) was not inhibited and only cough sensitive to coughreflux due to airway inflammation was inhibited. This feature seems tobe distinct from that of a central nervous system acting antitussiveagent such as dihydrocodeine that inhibits all the necessary cough.

Note that post of (a) or (c) in FIG. 4 shows, compared with the case ofcompound A, the results of the control group in which purified water wasadministered beforehand (at 1 h before citric acid stimulation) to thesham group mice or the airway inflammation group mice, respectively.

Example 6

To Evaluate Medicament Efficacy of Compound A by Local Application UsingNebulizer.

FIGS. 5 and 6 show the results of evaluating medicament efficacy ofcompound A by local application using a nebulizer instead of orallyadministration. At that time, ICR strain mice were used as the mice.Here, FIG. 6 shows an inhibition rate while the rate obtained from theresults (FIG. 5 ) of this Example was 0% when the number of coughs wasneither increased nor decreased and the rate was 100% when the number ofcoughs was 0.

(Test Results)

Control group mice (post of (a) in FIG. 5 ) in which nebulizer-processedpurified water was given, by inhalation, to pretreatment mice (the pregroup in FIG. 5 ) or test group mice in which compound A in aconcentration of 10 μg/mL (post of (b) in FIG. 5 ), 30 μg/mL (post of(c) in FIG. 5 ), or 100 μg/mL (post of (d) in FIG. 5 ) was given, byinhalation, to pretreatment mice were stimulated using a nebulizer with0.25 M citric acid after 4 min to trigger cough.

As a result, the local application of compound A elicited an antitussiveeffect, in a dose-dependent manner, more strongly and more rapidly usinga lower dose than the case of oral administration.

Example 7

(P2X4 Receptor Antagonistic Action)

The P2X4 receptor antagonistic action of compounds of the presentinvention was measured.

(Test Protocol)

The same protocol as of Example 1 was used to measure P2X4 receptorantagonistic action. Table 132 shows the results.

(Test Results)

TABLE 132 Test substance IC50 (μM) Compound F2 0.75 Compound F20 1.20Compound F48 (Compound B) 0.30 Compound F57 0.72 Compound F71 0.40Compound F106 1.80 Compound F118 1.10 Compound F173 0.06 Compound F1960.97 Compound F197 0.44 Compound F208 1.30 Compound F209 0.94 CompoundF210 1.40 Compound F214 0.62

Example 8

(P2X4 Receptor Antagonistic Action)

The P2X4 receptor antagonistic action of compounds of the presentinvention was measured.

(Test Protocol)

The same protocol as of Example 1 was used to measure P2X4 receptorantagonistic action. Table 133 shows the results.

(Test Results)

TABLE 133 Test compound Inhibitory action IC50 (μM) Compound G15 0.88

Example 9

(To Test Antitussive Action of Compound A in Guinea Pigs)

To test the presence or absence of antitussive action of compound A inaccordance with the (Cough Reflux-measuring Procedure) described inExample 3, guinea pigs that had orally received purified water orcompound A in an amount of 1, 3, or 10 mg/kg were stimulated with citricacid using a nebulizer at 1 h after the administration to induce coughreflux. In this way, the effects were investigated.

At that time, Hartly strain guinea pigs were used as the guinea pigs,and 0.5 M citric acid was used as the citric acid.

(Test Results)

FIGS. 7 and 8 show the results obtained.

The pre group in FIG. 7 shows the number of coughs after Hartly strainguinea pigs that had been given neither treatment nor administrationwere stimulated with 0.5 M citric acid. The post group in FIG. 7 showsthe number of coughs after the guinea pigs in which purified water or 1,3, or 10 mg/kg of compound A had been orally administered beforehand (at1 h before citric acid administration) to the pretreatment guinea pigswere stimulated with 0.5 M citric acid.

Note that as used herein, the “pretreatment guinea pigs” are referred toas guinea pigs that have been given neither treatment noradministration; the “control group guinea pigs” are referred to asguinea pigs in which purified water has been administered topretreatment guinea pigs; and the “test group guinea pigs” are referredto as guinea pigs in which a test subject compound has been administeredto pretreatment guinea pigs.

In addition, FIG. 8 shows an inhibition rate while the rate obtainedfrom the results (FIG. 7 ) of this Example was 0% when the number ofcoughs was neither increased nor decreased and the rate was 100% whenthe number of coughs was 0.

These results have demonstrated that compound A inhibited citricacid-induced cough in a dose-dependent manner and elicited a significantinhibitory action at 1 mg/kg or higher.

Example 10

(To Test Antitussive Action of Compound B in Guinea Pigs)

To test the presence or absence of antitussive action of compound B inaccordance with the (Cough Reflux-measuring Procedure) described inExample 3, guinea pigs that had orally received purified water orcompound B in an amount of 1, 3, 10, or 30 mg/kg were stimulated withcitric acid using a nebulizer at 1 h after the administration to inducecough reflux. In this way, the effects were investigated.

At that time, Hartly strain guinea pigs were used as the guinea pigs,and 0.5 M citric acid was used as the citric acid.

(Test Results)

FIGS. 9 and 10 show the results obtained.

The pre group of FIG. 9 shows the results of inducing cough reflux bystimulating pretreatment guinea pigs with 0.5 M citric acid. Inaddition, the post group of FIG. 9 shows the results of inducing coughreflux by stimulating, with 0.5 M citric acid, control group guinea pigsor test group guinea pigs in which purified water or 1, 3, 10, or 30mg/kg of compound B had been orally administered beforehand (at 1 beforecitric acid administration) to the pretreatment guinea pigs.

FIG. 10 shows an inhibition rate while the rate obtained from theresults (FIG. 9 ) of this Example was 0% when the number of coughs wasneither increased nor decreased and the rate was 100% when the number ofcoughs was 0.

As a result, compound B inhibited citric acid-induced cough in adose-dependent manner, and a significant inhibitory action was exhibitedat 1 mg/kg or higher.

Example 11

(To Produce OVA-Sensitized Cough Model Guinea Pigs)

When OVA, a foreign antigen, is inhaled, airway inflammation accompaniedby eosinophil infiltration is induced. Consequently, OVA-sensitizedguinea pigs present symptoms of allergic cough and atopic cough. Thus,the guinea pigs have been widely used as a pathological model(antigen-induced airway inflammation model animals) reflecting humanclinical conditions. Here, in the Examples of the present application,whether a compound(s) of the present application elicited coughinhibitory action against the pathological model was evaluated.

The OVA-sensitized cough model guinea pigs were produced specifically bythe following procedure.

Note that in the following procedure, Ovalbumin or mepyramine maleate isdissolved in saline and then used.

The number of citric acid-induced coughs is measured. Then, a mixture of200 μL of 0.05% OVA (Ovalbumin) and 100 μL of Imject Alum (prepared bysuspending aluminum hydroxide and magnesium hydroxide, each at aconcentration of 40 mg/mL, in water and by adding an inactivatingstabilizer thereto) per guinea pig is administered intraperitoneally(i.p.).

After the intraperitoneal administration, 0.5% OVA is given for 5 min byinhalation at days 7, 14, 21, and 28.

Note that at 30 min before the inhalation, mepyramine maleate (10 mg/kg)is given i.p. to prevent a shock symptom.

At Day 35, 0.5% ovalbumin is given for 60 min by inhalation. Note thatat 30 min before the inhalation, mepyramine maleate (10 mg/kg) is giveni.p. to prevent a shock symptom.

The next day of the final 0.5% ovalbumin challenge (day 35), the test isconducted.

Example 12

(Effects of Compound a on OVA Sensitization-Induced Cough in GuineaPigs)

FIG. 11 shows the results of investigating medicament efficacy ofcompound A on OVA sensitization-induced cough in a guinea pigOVA-sensitized cough model, which is a pathological model reflectingclinical conditions.

(Test Results)

OVA-sensitized cough model guinea pigs were used and stimulated with0.25 M citric acid by the same procedure as of Example 9 to induce coughreflux. For guinea pigs used in this Example, Hartly strain guinea pigswere used for any of the below-described pretreatment guinea pigs, shamgroup guinea pigs, and OVA-sensitized cough group guinea pigs.

Compared to a case where pretreatment guinea pigs (pre1 of (a), (b),(c), and (d) in FIG. 11 ) were stimulated with 0.25 M citric acid toinduce cough reflux, a case of guinea pigs (hereinafter, herein referredto as “sham group guinea pigs”; (a) and (b) in FIG. 11 ) where thepretreatment guinea pigs were nasally instilled with saline instead ofOVA and then stimulated with 0.1 M citric acid in accordance with theprocedure of Example 11 had no observed change in the number of coughs(pre2 of (a) and (b) in FIG. 11 ).

By contrast, when OVA-sensitized cough model guinea pigs (hereinafter,herein referred to as “OVA-sensitized cough group guinea pigs”; (c) and(d) in FIG. 11 ) produced from the pretreatment guinea pigs by theprocedure in Example 11 were stimulated with 0.1 M citric acid, anincrease in cough response was observed (pre2 of (c) and (d) in FIG. 11).

When 1 mg/kg of compound A was orally administered beforehand (at 1 hbefore citric acid stimulation) to the OVA-sensitized cough group guineapigs being sensitive to this cough stimulation, the cough responseincreased due to airway inflammation was inhibited completely (post of(d) in FIG. 11 ). On the contrary, when 1 mg/kg of compound A was orallyadministered beforehand (at 1 h before citric acid stimulation) to thesham group guinea pigs, a change in the number of coughs was unobserved(post of (b) in FIG. 11 ).

Note that post of (a) or (c) in FIG. 11 shows, compared with the case ofcompound A, the results of the control group in which purified water wasadministered beforehand (at 1 h before citric acid stimulation) to thesham group guinea pigs or the OVA-sensitized cough group guinea pigs,respectively.

The above results have revealed, even in the pathological modelreflecting clinical conditions, that cough necessary for biologicaldefense (0.25 M citric acid-induced cough) was not inhibited and onlycough sensitive to cough reflux due to airway inflammation wasinhibited. This feature seems to be distinct from that of a centralnervous system acting antitussive agent such as dihydrocodeine thatinhibits all the necessary cough.

Example 13

(Effects of Compound B on OVA Sensitization-Induced Cough in GuineaPigs)

FIG. 12 shows the results of investigating medicament efficacy ofcompound B on OVA sensitization-induced cough in a guinea pigOVA-sensitized cough model, which is a pathological model reflectingclinical conditions.

(Test Results)

OVA-sensitized cough model guinea pigs were used and stimulated with0.25 M citric acid by the same procedure as of Example 10 to inducecough reflux. For guinea pigs used in this Example, Hartly strain guineapigs were used for any of the below-described pretreatment guinea pigs,sham group guinea pigs, and OVA-sensitized cough group guinea pigs.

Compared to a case where pretreatment guinea pigs (pre1 of (a), (b),(c), and (d) in FIG. 12 ) were stimulated with 0.25 M citric acid toinduce cough reflux, a case of sham group guinea pigs ((a) and (b) inFIG. 12 ) that had received 0.1 M citric acid stimulation had noobserved change in the number of coughs (pre2 of (a) and (b) in FIG. 11).

By contrast, when OVA-sensitized cough group guinea pigs ((c) and (d) inFIG. 12 ) are stimulated with 0.1 M citric acid, an increase in coughresponse is observed (pre2 of (c) and (d) in FIG. 12 ).

When 1 mg/kg of compound B was orally administered beforehand (at 1 hbefore citric acid stimulation) to the OVA-sensitized cough group guineapigs being sensitive to this cough stimulation, the cough responseincreased due to airway inflammation was inhibited completely (post of(d) in FIG. 12 ). On the contrary, when 1 mg/kg of compound B was orallyadministered beforehand (at 1 h before citric acid stimulation) to thesham group guinea pigs, a change in the number of coughs was unobserved(post of (b) in FIG. 12 ).

Further, 1 mg/kg of compound B does not elicit any significantmedicament efficacy in the investigation of Example 10 (FIG. 10 ).

Note that post of each of (a) or (c) in FIG. 12 shows, compared with thecase of compound B, the results of the control group in which purifiedwater was administered beforehand (at 1 h before citric acidstimulation) to the sham group guinea pigs or the OVA-sensitized coughgroup guinea pigs, respectively.

The above results have revealed, even in the pathological modelreflecting clinical conditions, that cough necessary for biologicaldefense (0.25 M citric acid-induced cough) was not inhibited and onlycough sensitive to cough reflux due to airway inflammation wasinhibited. This feature seems to be distinct from that of a centralnervous system acting antitussive agent such as dihydrocodeine thatinhibits all the necessary cough.

Example 14

(P2X4 Receptor Antagonistic Action)

The P2X4 receptor antagonistic action of compounds of the presentinvention was measured.

(Test Protocol)

The same protocol as of Example 1 was used to measure P2X4 receptorantagonistic action. Tables 134 to 136 show the results.

(Test Results)

TABLE 134 Test compound Inhibitory action IC50 (μM) Compound H1 0.025Compound H2 0.037 Compound H4 0.044 Compound H11 0.077 Compound H210.078

TABLE 135 Test compound Inhibitory action IC50 (μM) Compound H22 0.091Compound H25 0.082 Compound H27 0.078 Compound H31 0.051 Compound H370.079 Compound H42 0.092 Compound H43 0.053 Compound H47 0.094

TABLE 136 Test compound Inhibitory action IC50 (μM) Compound H61 0.074Compound H62 0.088 Compound H67 0.053 Compound H79 0.039 Compound H830.087

Example 15

(Effects of Compound C or Compound D on Citric Acid-Induced Cough inGuinea Pigs)

Hartly strain guinea pigs that had been given neither treatment noradministration (pretreatment guinea pigs) were stimulated with citricacid to induce cough reflux. Then, the effects were investigated. FIG.13 shows the results of investigating medicament efficacy of compound Cor compound D on cough reflux induced by citric acid stimulation.

(Method)

To test, by using pretreatment guinea pigs, the presence or absence ofantitussive action of compound C or D in accordance with the (CoughReflux-measuring Procedure) described in Example 3, guinea pigs that hadorally received purified water or compound C in an amount of 58.8 mg/kgor compound D in an amount of 30 mg/kg were stimulated with citric acidusing a nebulizer at 1 h after the administration to induce coughreflux. In this way, the effects were investigated. Here, 0.5 M citricacid was used as the pretreated citric acid.

(Test Results)

FIG. 13 shows the results obtained.

A change in the number of coughs was unobserved between the coughresponse (pre of (a) in FIG. 13 ) of pretreatment guinea pigs ((a) to(c) in FIG. 13 ) when stimulated with 0.5 M citric acid and the coughresponse (post of (a) in FIG. 13 ) of the pretreatment guinea pigs towhich purified water was orally administered beforehand (at 1 h beforecitric acid stimulation) and 0.5 M citric acid stimulation was thengiven.

By contrast, the number of coughs was significantly decreased betweenthe cough response (pre of (b) in FIG. 13 ) of the pretreatment guineapigs when stimulated with 0.5 M citric acid and the cough response (postof (b) in FIG. 13 ) of the pretreatment guinea pigs to which 58.8 mg/kgof compound C was orally administered beforehand (at 1 h before citricacid stimulation) and 0.5 M citric acid stimulation was then given. LikeExamples 12 and 13, the cough response increased due to airwayinflammation was demonstrated to be inhibited completely.

Likewise, the number of coughs was significantly decreased between thecough response (pre of (c) in FIG. 13 ) of the pretreatment group guineapigs when stimulated with 0.5 M citric acid and the cough response (postof (c) in FIG. 13 ) of the pretreatment guinea pigs to which 30 mg/kg ofcompound D was orally administered beforehand (at 1 h before citric acidstimulation) and 0.5 M citric acid stimulation was then given. LikeExamples 12 and 13, compound D has been demonstrated to completelyinhibit the cough response increased due to airway inflammation.

In addition, FIG. 14 shows an inhibition rate while the rate obtainedfrom the results ((b) and (c) of FIG. 13 ) of this Example was 0% whenthe number of coughs was neither increased nor decreased and the ratewas 100% when the number of coughs was 0.

The above results have revealed, even in the pathological modelreflecting clinical conditions, that compound C or D does not inhibitcough necessary for biological defense (0.5 M citric acid-induced cough)and does inhibit only cough sensitive to cough reflux due to airwayinflammation. This feature seems to be distinct from that of a centralnervous system acting antitussive agent such as dihydrocodeine thatinhibits all the necessary cough.

Example 16 Synthesis of 5-[3 (1H-Tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione Sodium Salt

Here, 5-[3 (1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione, which is described in Example 1of WO 2010/093061, was obtained with reference to the process of Example2(2) disclosed in WO 2012/008478 to produce the titled compound.

¹H NMR (DMSO-d₆, 400 MHz) δ:3.17 (1H, d, J=12 Hz), 3.73 (1H, d, J=12Hz), 7.05 (1H, d, J=9 Hz), 7.19 (1H, d, J=9 Hz), 7.47 (1H, t, J=8 Hz),7.5-7.7 (4H, m), 7.88 (1H, d, J=8 Hz), 7.93 (1H, d, J=8 Hz), 8.26 (1H,d, J=8 Hz), 10.92 (1H, br s)

Example 17 Synthesis of5-[3-(1H-Tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-oneSodium Salt

Here,5-(3-Hydroxyphenyl)-1,3-dihydro-2H-naphtho[1,2-e]-1,4-diazepin-2-oneobtained by the process described in Example 2 of WO 2008/023847 wasobtained in reference to the synthesis scheme (method 3) described in WO2010/093061 or the process (synthesis method 2) described inparagraphs[0054] to [0060] of WO 2012/017876 to produce5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-one.Here,5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-onewas obtained with reference to the process of Example 2(2) disclosed inWO 2012/008478 to produce the titled compound.

¹H NMR (DMSO-d₆, 400 MHz) δ:3.81 (1H, d, J=9 Hz), 4.60 (1H, d, J=9 Hz),7.21 (1H, d, J=8 Hz), 7.4-7.5 (2H, m), 7.6-7.8 (3H, m), 7.9-8.2 (3H, m),8.3-8.5 (1H, m), 10.85 (1H, br s)

Example 18 Synthesis of5-[4-Fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dioneSodium Salt

Synthesis method 3 (paragraph[0043]) of synthesis scheme described in WO2013/105608 or the synthesis scheme (method 3) described in WO2010/093061 was referenced to produce5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione.Here,5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dionewas obtained with reference to the process of Example 2(2) disclosed inWO 2012/008478 to produce the titled compound.

¹H NMR (DMSO-d₆, 400 MHz) δ:3.12 (1H, d, J=12 Hz), 3.97 (1H, d, J=12Hz), 7.01 (1H, d, J=9 Hz), 7.2-7.4 (2H, m), 7.6-7.7 (4H, m), 7.87 (1H,d, J=8 Hz), 8.22 (1H, d, J=9 Hz), 10.89 (1H, br s)

Example 19

A medicament of the present invention can be prepared as a capsule asfollows.

Compound A, lactose, corn starch, and low-substitutedhydroxypropylcellulose can be charged into a V-type mixer and mixed toobtain a capsule formulation.

Components in 270 mg of granules

Compound A: 100 mg, lactose: 94 mg, corn starch: 40 mg, low-substitutedhydroxypropylcellulose: 21 mg, and hydroxypropylcellulose: 15 mg.

Here, 270 mg of the resulting capsule formulation can be manually filledinto No. 3 capsule to give a capsule.

In addition, any of compounds B to D can be likewise processed to give acapsule.

Example 20

A medicament of the present invention can be prepared as a nebulizerformulation as follows.

Compound A can be dissolved in sterile purified water to make a 10 to100 μg/mL solution. Next, 9 mg/mL NaCl solution can be added thereto toprepare a nebulizer formulation.

Example 21

(Action of Compound A on Contraction of Tracheobronchial Smooth MusclesExcised from Guinea Pig)

(Test Protocol)

An animal was sacrificed by phlebotomy while the ventral aorta wasdissected under urethane (2 g/kg, i.p.) anesthesia. Then, a left majorbronchial tissue was excised. After a connective tissue and bloodvessels were removed, each ring specimen with a width of about 3 mm wasprepared and suspended in an organ bath. Then, the isometric tension wasmeasured while the resting tension was set to 1.0 g. After the baselinetension was stabilized, whether each ring specimen was subject to anacetylcholine (ACh: 10⁻³ M)-mediated contraction reaction was verified.Then, the following mater was investigated.

The ACh-inducible contractile muscles were used to mimic airwaycontraction during parasympathetic excitation in vitro, and action ofcompound A on the contraction reaction was observed. Water was used as asolvent for compound A, which was then used at the final concentrationof 10⁻⁵ M.

(Test Results)

Compound A (at 10⁻⁵ M) did not affect the baseline tension or 10⁻⁵ MAch-induced contraction reaction (about 50% contraction of the maximumcontraction) of bronchial smooth muscle. FIG. 15 shows the resultsobtained.

Example 22

(Action of Compound B on Contraction of Tracheobronchial Smooth MusclesExcised from Guinea Pig)

(Test Protocol)

An animal was sacrificed by phlebotomy while the ventral aorta wasdissected under urethane (2 g/kg, i.p.) anesthesia. Next, a tracheal orleft major bronchial tissue was excised. After a connective tissue andblood vessels were removed, each ring specimen with a width of about 3mm was prepared and suspended in an organ bath. Then, the isometrictension was measured while the resting tension was set to 1.0 g. Afterthe baseline tension was stabilized, whether each ring specimen wassubject to an acetylcholine (ACh: 10⁻³ M)-mediated contraction reactionwas verified. Then, the following mater was investigated.

The Ach-inducible contractile muscles were used to mimic airwaycontraction during parasympathetic excitation in vitro, and action ofcompound B on the contraction reaction was observed. DMSO at the finalconcentration of 0.1% was used as a solvent for compound B. After 10⁻⁵ MACh-induced contraction reaction (about 50% contraction of the maximumcontraction) was stabilized, the specimen was treated with 10⁻⁶ Mcompound B (in DMSO at final 0.1%). The specimen was likewise treatedwith just 0.1% DMSO.

(Test Results)

Neither 0.1% DMSO itself, which was a solvent, nor compound B (at 10⁻⁶M) affected the ACh-induced contraction of bronchial smooth muscle. FIG.16 shows the results obtained.

INDUSTRIAL APPLICABILITY

A medicament of the present invention is useful as a medicament forpreventing or treating cough, preferably acute cough, persistent cough,or chronic cough and more preferably chronic cough, and should befurther highly effective in prophylaxis or treatment of cough such as adisease responsible for chronic cough including dry cough (e.g., coughcaused by cough variant asthma, atopic cough, cough caused bygastroesophageal reflux, chemical-induced cough, or allergic cough) orwet cough (e.g., cough caused by sinobronchial syndrome, cough caused bychronic bronchitis, cough caused by chronic obstructive pulmonarydisease, or cough caused by asthma). The medicament is useful, inparticular, for dry cough, and is especially useful for cough caused bycough variant asthma, atopic cough, or allergic cough.

1. A method for treating cough, the method comprising administering, toa subject in need thereof, a therapeutically effective amount of acompound having P2X4 receptor antagonistic action, or pharmaceuticallyacceptable salt thereof, wherein the compound having P2X4 receptorantagonistic action is a compound being selected from the groupconsisting of: (1) a compound having the following formula FI orpharmaceutically acceptable salt thereof; (2) a compound having thefollowing formula AI or pharmaceutically acceptable salt thereof; (3) acompound having the following formula GI or pharmaceutically acceptablesalt thereof; (4) a compound having the following formula HI orpharmaceutically acceptable salt thereof; (5) a compound having thefollowing formula HII or pharmaceutically acceptable salt thereof; (6) acompound having the following formula EI or pharmaceutically acceptablesalt thereof; and (7) a compound having the following formula BI orpharmaceutically acceptable salt thereof:

wherein R^(1F) and R^(2F) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), an optionally substituted phenyl group, an optionallysubstituted pyridyl group, or an aralkyl group (the number of carbonatoms in an aryl moiety is from 6 to 10 and the number of carbon atomsin an alkylene moiety is from 1 to 8), or R^(1F) and R^(2F) areoptionally fused with a benzene ring bonded thereto to form a condensedring selected from a naphthalene ring, a quinoline ring, an isoquinolinering, a tetrahydronaphthalene ring, an indane ring, atetrahydroquinoline ring, or a tetrahydroisoquinoline ring and a ringfused with R^(1F) and R^(2F) and comprising carbon atoms bonded torespective R^(1F) and R^(2F) is optionally substituted with 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),R^(3F) and R^(4F) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, a nitro group, a cyano group, an amino group, a C₁₋₈ alkylaminogroup, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxylgroup, a C₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbonatoms in an alkoxy moiety is from 1 to 8), or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8), R^(5F) representsa hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C₁₋₈alkyl group, or an aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 8), R^(6F) and R^(7F) are the same or different andrepresent a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, or an amino group, X^(F) represents C,or CH, Y^(F) represents N, or NH, a double line composed of a solid lineand a dashed line denotes a single bond or a double bond, Z^(F)represents an oxygen atom or a sulfur atom, A^(F) represents a bond orrepresents a benzene ring, a pyridine ring, a thiophene ring, apyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ringoptionally having, as substituents, 1 to 4 substituents, which are thesame or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),a phenyl group, or a pyridyl group, B^(F) represents N(R^(8F))C(═O),NHCONH, CON(R^(9F)), NHC(═S)NH, N(R^(10F))SO₂, SO₂N(R^(11F)), or OSO₂,R^(8F), R^(9F), R^(10F), and R^(11F) here represent a hydrogen atom, aC₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a hydroxyl-substituted C₁₋₈ alkyl group, or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8), D^(F) representsa bond or a C₁₋₆ alkylene chain optionally having, as substituents, 1 to4 substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a hydroxyl-substituted C₁₋₈ alkyl group, or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8)and further optionally having a double bond, E^(F) represents O, S,NR^(12F), or a bond, R^(12F) here represents a hydrogen atom, a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkyl group substituted with 1to 3 halogen atoms, a hydroxyl-substituted C₁₋₈ alkyl group, or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),G^(F) represents piperazine, piperidine, morpholine, cyclohexane,benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene,imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine orpyrimidine optionally having, as substituents, 1 to 4 substituents,which are the same or different, selected from a C₁₋₈ alkyl group, aC₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acyl group, a methylenedioxy group, a carboxyl group, aC₁₋₆ alkylsulfinyl group, a C₁₋₆ alkylthio group, a C₁₋₆ alkylsulfonylgroup, an aralkyl group (the number of carbon atoms in an aryl moiety isfrom 6 to 10 and the number of carbon atoms in an alkylene moiety isfrom 1 to 8), an optionally substituted phenyl, an optionallysubstituted pyridyl group, an optionally substituted imidazolyl group,an optionally substituted oxazolyl group, or an optionally substitutedthiazolyl group, and m^(F) represents an integer of 0 to 5, providedthat a case is excluded where R^(1F) and R^(2F) are not fused to form aring and where X^(F) is C, Y^(F) is N, the double line composed of asolid line and a dashed line denotes a double bond, Z^(F) is an oxygenatom, A^(F) is a benzene ring, m^(F) is 0, B^(F) is C(═O)NH, E^(F) is abond, and G^(F) is a phenyl group;

wherein R^(1A) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,or a phenyl-substituted C₁₋₃ alkyl group, R^(2A) and R^(3A) are the sameor different and represent a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a C₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, aC₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,R^(4A) and R^(5A) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, or a phenyl-substituted C₁₋₃ alkyl group, W^(A)represents an optionally substituted, 5- or 6-membered heterocyclic ringcomprising 1 to 4 atoms of nitrogen as a ring constituent element, andX^(A) is C, Y^(A) is N and a double line composed of a solid line and adashed line denotes a double bond;

wherein R^(1G), R^(2G), and R^(3G) are the same or different andrepresent a hydrogen atom, a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group,a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substitutedwith 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitrogroup, a cyano group, an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈dialkylamino group, X^(G) represents C, Y^(G) represents N, a doubleline composed of a solid line and a dashed line denotes a single bond ora double bond, n^(G) represents an integer of 0 to 6, Z^(G) representsO, S, or a bond, and A^(G) represents a benzene ring, a pyridine ring, apiperazine ring, a piperidine ring, or a morpholine ring optionallyhaving, as substituents, 1 to 5 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group, aC₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, or N(R^(4G))(R^(5G))where R^(4G) and R^(5G) are the same or different and represent a C₁₋₈alkyl group or R^(4G) and R^(5G) and a nitrogen atom bonded to R^(4G)and R^(5G) are fused to represent a 5- to 7-membered ring furtheroptionally comprising, as a ring forming atom, an oxygen atom or asulfur atom as a heteroatom;

wherein R^(1H) and R^(2H) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a C₂₋₈ acylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), an optionally substituted phenyl group, an optionallysubstituted pyridyl group, or an aralkyl group (the number of carbonatoms in an aryl moiety is from 6 to 10 and the number of carbon atomsin an alkylene moiety is from 1 to 8), or R^(1H) and R^(2H) areoptionally fused with a benzene ring bonded thereto to form a condensedring selected from a naphthalene ring, a quinoline ring, an isoquinolinering, a tetrahydronaphthalene ring, an indane ring, atetrahydroquinoline ring, or a tetrahydroisoquinoline ring and a ringfused with R^(1H) and R^(2H) and comprising carbon atoms bonded torespective R^(1H) and R^(2H) is optionally substituted with 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (thenumber of carbon atoms in an alkoxy moiety is from 1 to 8), or anaralkyl group (the number of carbon atoms in an aryl moiety is from 6 to10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),R^(3H) and R^(4H) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, aC₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxygroup substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxylgroup, a nitro group, a cyano group, an amino group, a C₁₋₈ alkylaminogroup, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxylgroup, a C₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbonatoms in an alkoxy moiety is from 1 to 8), or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8), R^(5H) representsa hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C₁₋₈alkyl group, or an aralkyl group (the number of carbon atoms in an arylmoiety is from 6 to 10 and the number of carbon atoms in an alkylenemoiety is from 1 to 8), R^(6H) and R^(7H) are the same or different andrepresent a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, or an amino group, X^(H) represents C,Y^(H) represents N, a double line composed of a solid line and a dashedline denotes a single bond or a double bond, Z^(H) represents O, S, orNH, A^(H) represents a benzene ring, a pyridine ring, a pyrimidine ring,a pyridazine ring, a thiophene ring, a furan ring, a pyrazole ring, animidazole ring, a quinoline ring, a benzimidazole ring, or an indanering optionally having, as substituents, 1 to 4 substituents, which arethe same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group,B^(H) represents O, S, NR⁸H, or a bond, R^(8H) here represents ahydrogen atom or a C₁₋₈ alkyl group, D^(H) represents a benzene ring, apyridine ring, a pyrimidine ring, a pyridazine ring, a thiophene ring, afuran ring, a tetrazole ring, an imidazole ring, an imidazoline ring, atriazole ring, a thiazole ring, an oxazole ring, an isoxazole ring, apyrazole ring, a pyrrole ring, a pyrrolidine ring, a piperazine ring, apiperidine ring, or a 5- to 8-membered cycloalkyl ring optionallyhaving, as substituents, 1 to 4 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group, E^(H)represents —(CR^(9H)R^(10H))_(n) ^(H)-T-, R^(9H) and R^(10H) here arethe same or different and represent a hydrogen atom, a hydroxyl group,or a C₁₋₈ alkyl group, or R^(9H) and R^(10H) are optionally fused toform an ethylene chain, n^(H) represents an integer of 0 to 8, T^(H)represents O, S, NR^(11H), or a bond, R^(11H) here represents a hydrogenatom or a C₁₋₈ alkyl group, G^(H) represents a benzene ring, a pyridinering, an imidazole ring, a pyrrole ring, a pyrazole ring, a thiophenering, a furan ring, a thiazole ring, an oxazole ring, a pyrimidine ring,a pyridazine ring, a pyrazine ring, a naphthalene ring, a quinolinering, a quinazoline ring, an indole ring, an indoline ring, a piperazinering, a piperidine ring, a morpholine ring, or a 5- to 8-memberedcycloalkyl ring optionally having, as substituents, 1 to 5 substituents,which are the same or different, selected from a C₁₋₈ alkyl group, aC₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substitutedwith 1 to 3 halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyanogroup, an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylaminogroup, a carbamoyl group, or a methanesulfonyl group, and m^(H)represents an integer of 0 to 2;

wherein R^(1Ha), R^(2Ha), R^(3Ha), R^(4Ha), R^(5Ha), and R^(6Ha) are thesame or different and represent a hydrogen atom, a C₁₋₈ alkyl group, aC₃₋₈ cycloalkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a carboxyl group, aC₂₋₈ acyl group, an alkoxycarbonyl group (the number of carbon atoms inan alkoxy moiety is from 1 to 8), an optionally substituted phenylgroup, an optionally substituted pyridyl group, or an aralkyl group (thenumber of carbon atoms in an aryl moiety is from 6 to 10 and the numberof carbon atoms in an alkylene moiety is from 1 to 8), X^(Ha) representsC, Y^(Ha) represents N, a double line composed of a solid line and adashed line denotes a single bond or a double bond, A^(Ha) represents abenzene ring, a pyridine ring, a pyrimidine ring, a pyridazine ring, athiophene ring, a furan ring, a pyrazole ring, an imidazole ring, aquinoline ring, a benzimidazole ring, or an indane ring optionallyhaving, as substituents, 1 to 4 substituents, which are the same ordifferent, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, aC₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogenatoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, ahalogen atom, a hydroxyl group, a nitro group, a cyano group, an aminogroup, a C₁₋₈ alkylamino group, or a C₂₋₈ dialkylamino group, D^(Ha)represents a benzene ring, a pyridine ring, a pyrimidine ring, apyridazine ring, a thiophene ring, a furan ring, a tetrazole ring, animidazole ring, an imidazoline ring, a triazole ring, a thiazole ring,an oxazole ring, an isoxazole ring, a pyrazole ring, a pyrrole ring, apyrrolidine ring, a piperazine ring, a piperidine ring, or a 5- to8-membered cycloalkyl ring optionally having, as substituents, 1 to 4substituents, which are the same or different, selected from a C₁₋₈alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈ alkylgroup substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group,or a C₂₋₈ dialkylamino group, E^(Ha) represents—(CR^(9Ha)R^(10Ha))_(p)-T^(Ha)-, R^(9Ha) and R^(10Ha) here are the sameor different and represent a hydrogen atom, a hydroxyl group, or a C₁₋₈alkyl group, or R^(9Ha) and R^(10Ha) are optionally fused to form anethylene chain, p represents an integer of 0 to 8, T^(Ha) represents O,S, NR^(11Ha), or a bond, R^(11Ha) here represents a hydrogen atom or aC₁₋₈ alkyl group, and G^(Ha) represents a benzene ring, a pyridine ring,an imidazole ring, a pyrrole ring, a pyrazole ring, a thiophene ring, afuran ring, a thiazole ring, an oxazole ring, a pyrimidine ring, apyridazine ring, a pyrazine ring, a naphthalene ring, a quinoline ring,a quinazoline ring, an indole ring, an indoline ring, a piperazine ring,a piperidine ring, a morpholine ring, or a 5- to 8-membered cycloalkylring optionally having, as substituents, 1 to 5 substituents, which arethe same or different, selected from a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, a C₁₋₈ alkoxy group substituted with 1 to 3 halogenatoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group,an amino group, a C₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, acarbamoyl group, or a methanesulfonyl group;

wherein R^(1E) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈alkenyl group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,or a phenyl-substituted C₁₋₃ alkyl group, R^(2E) and R^(3E) are the sameor different and represent a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈alkoxy group, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms,a C₁₋₈ alkoxy group substituted with 1 to 3 halogen atoms, a halogenatom, a hydroxyl group, a nitro group, a cyano group, an amino group, aC₁₋₈ alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylaminogroup, a C₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, aC₁₋₈ alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,R^(4E) and R^(5E) are the same or different and represent a hydrogenatom, a C₁₋₈ alkyl group, a C₁₋₈ alkyl group substituted with 1 to 3halogen atoms, or a phenyl-substituted C₁₋₃ alkyl group,

represents naphthalene or tetrahydronaphthalene, W^(2E) represents anoptionally substituted heterocyclic ring, X^(E) is C, Y^(E) is N and adouble line composed of a solid line and a dashed line denotes a doublebond, and P^(E) is 0 or 1;

wherein R^(1B) and R^(2B) are the same or different and represent ahydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxygroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, a C₂₋₈alkylamino group, a C₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, aC₂₋₈ acylamino group substituted with 1 to 3 halogen atoms, a C₁₋₈alkylsulfonylamino group, a carboxyl group, a C₂₋₈ acyl group, analkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety isfrom 1 to 8), a carbamoyl group, a C₁₋₈ alkylthio group, a C₁₋₈alkylsulfinyl group, a C₁₋₈ alkylsulfonyl group, or a sulfamoyl group,R^(3B) represents a hydrogen atom, a C₁₋₈ alkyl group, a C₂₋₈ alkenylgroup, a C₁₋₈ alkyl group substituted with 1 to 3 halogen atoms, or aphenyl-substituted C₁₋₃ alkyl group, R^(4B) and R^(5B) are the same ordifferent and represent a hydrogen atom, a C₁₋₈ alkyl group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a halogen atom, ahydroxyl group, a nitro group, a cyano group, an amino group, or aphenyl-substituted C₁₋₃ alkyl group, R^(6B) represents a hydrogen atom,a C₁₋₈ alkyl group, a C₂₋₈ alkenyl group, a C₁₋₈ alkoxy group, a C₁₋₈alkyl group substituted with 1 to 3 halogen atoms, a C₁₋₈ alkoxy groupsubstituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group,a nitro group, a cyano group, an amino group, a C₁₋₈ alkylamino group, aC₂₋₈ dialkylamino group, a C₂₋₈ acylamino group, a C₂₋₈ acylamino groupsubstituted with 1 to 3 halogen atoms, a C₁₋₈ alkylsulfonylamino group,a carboxyl group, a C₂₋₈ acyl group, an alkoxycarbonyl group (the numberof carbon atoms in an alkoxy moiety is from 1 to 8), a carbamoyl group,a C₁₋₈ alkylthio group, a C₁₋₈ alkylsulfinyl group, a C₁₋₈ alkylsulfonylgroup, a sulfamoyl group, an optionally substituted phenyl group, or anoptionally substituted heterocyclic ring group,

optionally contains, as ring constituent elements, 1 to 2 heteroatomsselected from N, S, or O and represents a 5- to 8-membered non-aromaticring condensed with a benzene ring at positions 1 and 2,

represents an aromatic ring selected from a benzene ring, a naphthalenering, a thiophene ring, a pyridine ring, a pyrimidine ring, an indolering, an indazole ring, a benzotriazole ring, a benzisoxazole ring, abenzimidazole ring, or a quinoline ring, Z^(B) represents O or S, andX^(B) is C, Y^(B) is N and a double line composed of a solid line and adashed line denotes a double bond.
 2. The method according to claim 1,wherein the compound having P2X4 receptor antagonistic action orpharmaceutically acceptable salt thereof is a compound or apharmaceutically acceptable salt being selected from the groupconsisting of: (A20)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-one;(A21)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-onesodium salt; (E6)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-one;(E7)5-[3-(1H-tetrazol-5-yl)phenyl]-1,3-dihydro-2H-naphtho[1,2-e][1,4]diazepin-2-onesodium salt; (F64)5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;(F69)5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;(F91)5-[4-(2-tert-butylbenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;(F135)5-[4-(2-chloro-6-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;(F137)5-[4-(2-chloro-6-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one;(F149)N-[3-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; (F197)1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]methanesulfonamide;(G1)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-3-(pyridin-2-yl)propionamide;(G2)2-ethyl-3-hydroxy-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]benzamide;(G3)2-ethyl-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]nicotinamidedihydrochloride; (G4)2-ethyl-6-hydroxy-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]benzamide;(G5)3-ethyl-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]picolinamidehydrochloride; (G6)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-2-(pyridin-2-yloxy)acetamidehydrochloride; (G7)2-(2-methoxyphenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]Acetamide;(G8)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)-phenyl]-3-(pyridin-3-yl)propionamidedihydrochloride; (G9)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]-3-phenylpropanamide;(G15)2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamide;(G16)2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamidedihydrochloride; (G17)2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedimethanesulfonate; (G19)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-2-(1H-pyrrole-1-yl)nicotinamidedihydrochloride; (G20)2-(morpholin-4-yl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]nicotinamidedihydrochloride; (G21)N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]-diazepin-5-yl)phenyl]-2-(pyrrolidine-1-yl)nicotinamidedihydrochloride; (G22)4-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamidedihydrochloride; (G23)2-isopropyl-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedihydrochloride; (G24)2-(isopropylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotineamidedihydrochloride; (H17)5-[4-[5-[2-(pyridin-2-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-onedihydrochloride; (H19)5-[4-[5-(2-methoxybenzyl)-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-one;(H39)5-[4-[5-[2-(pyridin-2-yl)ethyl]-1H-tetrazol-1-yl]phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-onedihydrochloride; (H40)5-[4-(5-phenethyl-1H-tetrazol-1-yl)phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-one; and (H41)5-[4-(2-phenethyl-1H-imidazol-1-yl)phenyl]-1H-naphtho[1,2-e][1,4]diazepin-2(3H)-one dihydrochloride.
 3. The method according to claim 1, whereinthe compound having P2X4 receptor antagonistic action orpharmaceutically acceptable salt thereof is1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]methanesulfonamide.4. The method according to claim 1, wherein the compound having P2X4receptor antagonistic action or pharmaceutically acceptable salt thereofis2-(dimethylamino)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]nicotinamidedihydrochloride.
 5. The method according to claim 1, wherein the coughis acute cough, persistent cough, or chronic cough.
 6. The methodaccording to claim 1, wherein the cough is chronic cough.
 7. The methodaccording to claim 1, wherein the cough is dry cough that is coughcaused by cough variant asthma, atopic cough, cough caused bygastroesophageal reflux, chemical-induced cough, or allergic cough. 8.The method according to claim 1, wherein the cough is dry cough that iscough caused by cough variant asthma, atopic cough, or allergic cough.9. The method according to claim 1, wherein the cough is wet cough thatis cough caused by sinobronchial syndrome, cough caused by chronicbronchitis, cough caused by chronic obstructive pulmonary disease, orcough caused by asthma.
 10. The method according to claim 1, which isperipheral cough suppression of dry cough.
 11. The method according toclaim 10, which is selective to the peripheral cough suppression of drycough.
 12. The method according to claim 11, wherein the dry cough iscough caused by cough variant asthma, atopic cough, or allergic cough.